生信网-文献期刊

Front Immunol

2023 Feb 28

Geng Z, Ye C, Zhu X.

2. Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing.

Front Immunol

2023 Feb 28

Gauthier V, Kyriazi M, Nefla M

3. Computer-aided classification of indirect immunofluorescence patterns on esophagus and split skin for the detection of autoimmune dermatoses.

Front Immunol

2023 Feb 28

Hocke J, Krauth J, Krause C

4. Recapitulating essential pathophysiological characteristics in lung-on-a-chip for disease studies.

Front Immunol

2023 Feb 28

Zhang Y, Wang X, Yang Y

5. Deciphering the potential roles of ferroptosis in regulating tumor immunity and tumor immunotherapy.

Front Immunol

2023 Feb 28

Gu X, Liu Y, Dai X

6. Blockade of endothelin-1 receptor B regulates molecules of the major histocompatibility complex in sickle cell disease.

Front Immunol

2023 Feb 28

Inostroza-Nieves Y, Rivera A, Romero JR.

7. Quantitative and causal analysis for inflammatory genes and the risk of Parkinson's disease.

Front Immunol

2023 Feb 28

Yi M, Li J, Jian S

8. Blood count derangements after sepsis and association with post-hospital outcomes.

Front Immunol

2023 Feb 28

Denstaedt SJ, Cano J, Wang XQ

RATIONALE: Predicting long-term outcomes in sepsis survivors remains a difficult task. Persistent inflammation post-sepsis is associated with increased risk for rehospitalization and death. As surrogate markers of inflammation, complete blood count parameters measured at hospital discharge may have prognostic value for sepsis survivors. OBJECTIVE: To determine the incremental value of complete blood count parameters over clinical characteristics for predicting 90-day outcomes in sepsis survivors. METHODS: Electronic health record data was used to identify sepsis hospitalizations at United States Veterans Affairs hospitals with live discharge and relevant laboratory data (2013 to 2018). We measured the association of eight complete blood count parameters with 90-day outcomes (mortality, rehospitalization, cause-specific rehospitalizations) using multivariable logistic regression models. MEASUREMENTS AND MAIN RESULTS: We identified 155,988 eligible hospitalizations for sepsis. Anemia (93.6%, N=142,162) and lymphopenia (28.1%, N=29,365) were the most common blood count abnormalities at discharge. In multivariable models, all parameters were associated with the primary outcome of 90-day mortality or rehospitalization and improved model discrimination above clinical characteristics alone (likelihood ratio test, p<0.02 for all). A model including all eight parameters significantly improved discrimination (AUROC, 0.6929 v. 0.6756) and reduced calibration error for the primary outcome. Hemoglobin had the greatest prognostic separation with a 1.5 fold increased incidence of the primary outcome in the lowest quintile (7.2-8.9 g/dL) versus highest quintile (12.70-15.80 g/dL). Hemoglobin and neutrophil lymphocyte ratio provided the most added value in predicting the primary outcome and 90-day mortality alone, respectively. Absolute lymphocyte count added little value in predicting 90-day outcomes. CONCLUSIONS: The incorporation of discharge complete blood count parameters into prognostic scoring systems could improve prediction of 90-day outcomes. Hemoglobin had the greatest prognostic value for the primary composite outcome of 90-day rehospitalization or mortality. Absolute lymphocyte count provided little added value in multivariable model comparisons, including for infection- or sepsis-related rehospitalization.

9. Appropriate pre-transplant strategy for patients with myelodysplastic syndromes receiving allogeneic haematopoietic stem cell transplantation after myeloablative conditioning.

Front Immunol

2023 Feb 28

Wang H, Wang Q, Qi J

10. An external quality assessment feasibility study; cross laboratory comparison of haemagglutination inhibition assay and microneutralization assay performance for seasonal influenza serology testing: A FLUCOP study.

Front Immunol

2023 Feb 28

Waldock J, Weiss CD, Wang W

11. The role of macrophage subsets in and around the heart in modulating cardiac homeostasis and pathophysiology.

Front Immunol

2023 Feb 28

Isidoro CA, Deniset JF.

12. Hypothermic machine perfusion alleviates ischemia-reperfusion injury of intestinal transplantation in pigs.

Front Immunol

2023 Feb 28

Hou W, Yang S, Lu J

13. Unique profile on the progress free survival and overall survival in patients with advanced non-small cell lung cancer in the Qujing area, Southwest China.

Front Immunol

2023 Feb 28

Ma Y, Shi H, Zhao G

BACKGROUND: China's southwestern region, Qujing, harbors a high incidence of non-small cell lung cancer (NSCLC) and related mortality. This study was designed to reveal the impact of an immune-related prognostic signature (IRPS) on advanced NSCLC in the Qujing. METHODS: Tissue specimens from an independent cohort of 37 patients with advanced NSCLC were retrospectively evaluated to determine the relationship between the IRPS estimated by next-generation sequencing (NGS) and clinical outcome. To compare the IRPS in tissue and the clinical outcomes between Qujing and non-Qujing populations, we analyzed datasets of 23 patients with advanced NSCLC from The Cancer Genome Atlas (TCGA) database. In addition, an independent cohort (n=111) of blood specimens was retrospectively analyzed to determine the relationship between the IRPS and clinical outcome. Finally, we evaluated the utility of the blood IRPS in classifying 24 patients with advanced NSCLC who might benefit from immunotherapy. RESULTS: In cohort 1, the Qujing population with tTMB-H (≥ 10 mutations/Mb) or KRAS mutations had shorter progression-free survival (PFS) (hazard ratio [HR] 0.37, 0.14 to 0.97, P = 0.04; HR 0.23, 0.08 to 0.66, P < 0.01) and overall survival (OS) (HR 0.05, 0.01 to 0.35, P < 0.01; HR 0.22, 0.07 to 0.66, P < 0.01). In cohort 2 of the Qujing population, bTMB-H (≥ 6 mutations per Mb) and KRAS mutations were related to PFS (HR 0.59, 0.36 to 0.99, P = 0.04; HR 0.50, 0.26 to 0.98, P = 0.04) and OS (HR 0.58, 0.35 to 0.96, P = 0.03; HR 0.48, 0.25 to 0.93, P = 0.03). Notably, the Qujing population with bTMB-H had superior PFS (HR 0.32, 0.09 to 1.09, P = 0.01), OS (HR 0.33, 0.10 to 1.13, P < 0.01) and objective response rates (ORRs) (83.3% vs. 14.3% vs. 20.0%, P <0.01) to immunotherapy than other populations. CONCLUSIONS: These findings show that tTMB, bTMB and KRAS mutations appear to be independent validated IRPSs that predict the clinical outcomes of Qujing populations with advanced NSCLC and that bTMB may be used as a reliable IRPS to predict the clinical benefit from anti-PD-1 therapies among populations from Qujing with advanced NSCLC.

14. New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF.

Front Immunol

2023 Feb 28

Liu ZY, Sun MX, Hua MQ

15. The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update.

Front Immunol

2023 Feb 28

Lotfi N, Yousefi Z, Golabi M

16. Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials.

Front Immunol

2023 Feb 28

Liu H, Luo SX, Jie J

17. Safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of WBP216, a novel IL-6 monoclonal antibody, in patients with rheumatoid arthritis: A phase Ia randomized placebo-controlled study.

Front Immunol

2023 Feb 28

Leng X, Tang X, Hu P

18. Immunomodulatory activity of manganese dioxide nanoparticles: Promising for novel vaccines and immunotherapeutics.

Front Immunol

2023 Feb 28

Huang Y, Ruan Y, Ma Y

19. Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice.

Front Immunol

2023 Feb 28

Aggarwal C, Ramasamy V, Garg A

20. cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging.

Front Immunol

2023 Feb 28

Schmitz CRR, Maurmann RM, Guma FTCR

21. Case report: Novel variants in RELA associated with familial Behcet's-like disease.

Front Immunol

2023 Feb 28

An JW, Pimpale-Chavan P, Stone DL

22. The role of mesenchymal stem cell-derived EVs in diabetic wound healing.

Front Immunol

2023 Feb 28

Jiang M, Jiang X, Li H

23. Evaluation of a renal risk score for Japanese patients with ANCA-associated glomerulonephritis in a multi-center cohort study.

Front Immunol

2023 Feb 28

Uchida T, Ichinose K, Yamashita A

24. Utility of laboratory and immune biomarkers in predicting disease progression and mortality among patients with moderate to severe COVID-19 disease at a Philippine tertiary hospital.

Front Immunol

2023 Feb 28

Punzalan FER, Aherrera JAM, de Paz-Silava SLM

PURPOSE: This study was performed to determine the clinical biomarkers and cytokines that may be associated with disease progression and in-hospital mortality in a cohort of hospitalized patients with RT-PCR confirmed moderate to severe COVID-19 infection from October 2020 to September 2021, during the first wave of COVID-19 pandemic before the advent of vaccination. PATIENTS AND METHODS: Clinical profile was obtained from the medical records. Laboratory parameters (complete blood count [CBC], albumin, LDH, CRP, ferritin, D-dimer, and procalcitonin) and serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IFN-γ, IP-10, TNF-α) were measured on Days 0-3, 4-10, 11-14 and beyond Day 14 from the onset of illness. Regression analysis was done to determine the association of the clinical laboratory biomarkers and cytokines with the primary outcomes of disease progression and mortality. ROC curves were generated to determine the predictive performance of the cytokines. RESULTS: We included 400 hospitalized patients with COVID-19 infection, 69% had severe to critical COVID-19 on admission. Disease progression occurred in 139 (35%) patients, while 18% of the total cohort died (73 out of 400). High D-dimer >1 µg/mL (RR 3.5 95%CI 1.83-6.69), elevated LDH >359.5 U/L (RR 1.85 95%CI 1.05-3.25), lymphopenia (RR 1.91 95%CI 1.14-3.19), and hypoalbuminemia (RR 2.67, 95%CI 1.05-6.78) were significantly associated with disease progression. High D-dimer (RR 3.95, 95%CI 1.62-9.61) and high LDH (RR 5.43, 95%CI 2.39-12.37) were also significantly associated with increased risk of in-hospital mortality. Nonsurvivors had significantly higher IP-10 levels at 0 to 3, 4 to 10, and 11 to 14 days from illness onset (p<0.01), IL-6 levels at 0 to 3 days of illness (p=0.03) and IL-18 levels at days 11-14 of illness (p<0.001) compared to survivors. IP-10 had the best predictive performance for disease progression at days 0-3 (AUC 0.81, 95%CI: 0.68-0.95), followed by IL-6 at 11-14 days of illness (AUC 0.67, 95%CI: 0.61-0.73). IP-10 predicted mortality at 11-14 days of illness (AUC 0.77, 95%CI: 0.70-0.84), and IL-6 beyond 14 days of illness (AUC 0.75, 95%CI: 0.68-0.82). CONCLUSION: Elevated D-dimer, elevated LDH, lymphopenia and hypoalbuminemia are prognostic markers of disease progression. High IP-10 and IL-6 within the 14 days of illness herald disease progression. Additionally, elevated D-dimer and LDH, high IP-10, IL-6 and IL-18 were also associated with mortality. Timely utilization of these biomarkers can guide clinical monitoring and management decisions for COVID-19 patients in the Philippines.

25. Cross-reactive antibodies against Langat virus protect mice from lethal tick-borne encephalitis virus infection.

Front Immunol

2023 Feb 28

Kubinski M, Beicht J, Zdora I

26. Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose.

Front Immunol

2023 Feb 28

Perico L, Todeschini M, Casiraghi F

27. Inflammatory myopathies and beyond: The dual role of neutrophils in muscle damage and regeneration.

Front Immunol

2023 Feb 27

Torres-Ruiz J, Alcalá-Carmona B, Alejandre-Aguilar R

Skeletal muscle is one of the most abundant tissues of the human body and is responsible for the generation of movement. Muscle injuries can lead to severe disability. Skeletal muscle is characterized by an important regeneration capacity, which is possible due to the interaction between the myoblasts and immune cells. Neutrophils are fundamental as inducers of muscle damage and as promoters of the initial inflammatory response which eventually allows the muscle repair. The main functions of the neutrophils are phagocytosis, respiratory burst, degranulation, and the production of neutrophil extracellular traps (NETs). An overactivation of neutrophils after muscle injuries may lead to an expansion of the initial damage and can hamper the successful muscle repair. The importance of neutrophils as inducers of muscle damage extends beyond acute muscle injury and recently, neutrophils have become more relevant as part of the immunopathogenesis of chronic muscle diseases like idiopathic inflammatory myopathies (IIM). This heterogeneous group of systemic autoimmune diseases is characterized by the presence of muscle inflammation with a variable amount of extramuscular features. In IIM, neutrophils have been found to have a role as biomarkers of disease activity, and their expansion in peripheral blood is related to certain clinical features like interstitial lung disease (ILD) and cancer. On the other hand, low density granulocytes (LDG) are a distinctive subtype of neutrophils characterized by an enhanced production of NETs. These cells along with the NETs have also been related to disease activity and certain clinical features like ILD, vasculopathy, calcinosis, dermatosis, and cutaneous ulcers. The role of NETs in the immunopathogenesis of IIM is supported by an enhanced production and deficient degradation of NETs that have been observed in patients with dermatomyositis and anti-synthetase syndrome. Finally, new interest has arisen in the study of other phenotypes of LDG with a phenotype corresponding to myeloid-derived suppressor cells, which were also found to be expanded in patients with IIM and were related to disease activity. In this review, we discuss the role of neutrophils as both orchestrators of muscle repair and inducers of muscle damage, focusing on the immunopathogenesis of IIM.

28. CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression.

Front Immunol

2023 Feb 27

Yang D, Zhao D, Ji J

INTRODUCTION: Circular RNAs (circRNAs) have been linked to regulate macrophage polarization and subsequent inflammation in sepsis. However, the underlying mechanism and the function of circRNAs in macrophage pyroptosis in pneumonia-induced sepsis are still unknown. METHODS: In this study, we screened the differentially expressed circRNAs among the healthy individuals, pneumonia patients without sepsis and pneumonia-induced sepsis patients in the plasma by RNA sequencing (RNA-seq). Then we evaluated macrophage pyroptosis in sepsis patients and in vitro LPS/nigericin activated THP-1 cells. The lentiviral recombinant vector for circ_0075723 overexpression (OE-circ_0075723) and circ_0075723 silence (sh-circ_0075723) were constructed and transfected into THP-1 cells to explore the potential mechanism of circ_0075723 involved in LPS/nigericin induced macrophage pyroptosis. RESULTS: We found circ_0075723, a novel circRNA that was significantly downregulated in pneumonia-induced sepsis patients compared to pneumonia patients without sepsis and healthy individuals. Meanwhile, pneumonia-induced sepsis patients exhibited activation of NLRP3 inflammasome and production of the pyroptosis-associated pro-inflammatory cytokines IL-1β and IL-18. circ_0075723 inhibited macrophage pyroptosis via sponging miR-155-5p which promoted SHIP1 expression directly. Besides, we found that circ_0075723 in macrophages promoted VE-cadherin expression in endothelial cells through inhibiting the release of NLRP3 inflammasome-related cytokines, IL-1β and IL-18, and protects endothelial cell integrity. DISCUSSION: Our findings propose a unique approach wherein circ_0075723 suppresses macrophage pyroptosis and inflammation in pneumonia-induced sepsis via sponging with miR-155-5p and promoting SHIP1 expression. These findings indicate that circRNAs could be used as possible potential diagnostic and therapeutic targets for pneumonia-induced sepsis.

29. Pan-cancer analysis reveals potential of FAM110A as a prognostic and immunological biomarker in human cancer.

Front Immunol

2023 Feb 27

Zhong H, Shi Q, Wen Q

BACKGROUND: Despite great success, immunotherapy still faces many challenges in practical applications. It was previously found that family with sequence similarity 110 member A (FAM110A) participate in the regulation of the cell cycle and plays an oncogenic role in pancreatic cancer. However, the prognostic value of FAM110A in pan-cancer and its involvement in immune response remain unclear. METHODS: The Human Protein Atlas (HPA) database was used to detect the expression of FAM110A in human normal tissues, the Tumor Immune Estimation Resource (TIMER) and TIMER 2.0 databases were used to explore the association of FAM110A expression with immune checkpoint genes and immune infiltration, and the Gene Set Cancer Analysis (GSCA) database was used to explore the correlation between FAM110A expression and copy number variations (CNV) and methylation. The LinkedOmics database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Statistical analysis and visualization of data from the The Cancer Genome Atlas (TCGA) or the Genotype-Tissue Expression (GTEx) databases were performed using the R software (version 3.6.3). Clinical samples were validated using immunohistochemistry. RESULTS: FAM110A expression was elevated in most tumor tissues compared with that in normal tissues. CNV and methylation were associated with abnormal FAM110A mRNA expression in tumor tissues. FAM110A affected prognosis and was associated with the expression of multiple immune checkpoint genes and abundance of tumor-infiltrating immune cells across multiple types of cancer, especially in liver hepatocellular carcinoma (LIHC). FAM110A-related genes were involved in multiple immune-related processes in LIHC. CONCLUSION: FAM110A participates in regulating the immune infiltration and affecting the prognosis of patients in multiple cancers, especially in LIHC. FAM110A may serve as a prognostic and immunological biomarker for human cancer.

30. The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles.

Front Immunol

2023 Feb 27

González-Rioja R, Salazar VA, Bastús NG

31. Association of normal weight obesity phenotype with inflammatory markers: A systematic review and meta-analysis.

Front Immunol

2023 Feb 27

Mohammadian Khonsari N, Baygi F, Tabatabaei-Malazy O

BACKGROUND: Individuals with normal weight could suffer from obesity based on their body fat percentage (also known as normal weight obesity (NWO)), thus being at risk of significant morbidity and mortality compared to the general population. It seems that inflammatory pathways and chronic inflammation are significant contributors to the pathogenicity of NWO. This study aimed to assess and pool the association of proinflammatory and anti-inflammatory cytokines with NWO. METHODS: In this systematic review and meta-analysis, online international databases (PubMed, Scopus, EMBASE, Web of Science, and Google Scholar) were searched until August 2022. All observational studies with an English full text comparing the mean levels of proinflammatory and anti-inflammatory cytokines (e.g., C-reactive protein (CRP), various types of interleukins (IL) s, tumor necrosis factor-alpha (TNF)) and white blood cell (WBC) count, in subjects with NWO and "normal weight non-obese (NWNO)" were included. Two researchers independently screened, reviewed and assessed the quality of included studies. The remaining articles' data were extracted post-screening. The heterogeneity between studies was assessed using the I2 and Cochran's Q tests. A random effect model meta-analysis was used to pool the standardized mean difference (SMD) as an effect size. RESULTS: From the initial 559 studies, 21 and 19 were included in the qualitative and quantitative synthesis, respectively. In the systematic review, 8 studies reported a significant association between various proinflammatory cytokines (CRP, IL6, IL1β, and TNFα) and NWO. According to random-effect meta-analysis, the association between NWO with CRP (SMD: 0.60, 95% CI: 0.30, 0.91) and IL6 (SMD: 0.90, 95%CI: 0.14, 1.66) was statistically significant. Moreover, the mean level of TNFα in subjects with NWO and NWNO did not differ significantly (SMD: 0.67, 95% CI: -0.36, 1.70). CONCLUSION: The findings of this study show that NWO was associated with high levels of CRP and IL6. Therefore, inflammatory pathways may play a role in the pathogenicity of NWO.

32. Case report: Spontaneous remission in lung carcinoma with a late relapse after adjuvant immunotherapy: Exceptional tumor micro-environment.

Front Immunol

2023 Feb 27

Chen Y, Guan W, Zhong C

33. Allergic adverse events following immunization: Data from post-marketing surveillance in Apulia region (South of Italy).

Front Immunol

2023 Feb 27

Stefanizzi P, Ferorelli D, Scazzi FL

34. Lactate exposure shapes the metabolic and transcriptomic profile of CD8+ T cells.

Front Immunol

2023 Feb 27

Barbieri L, Veliça P, Gameiro PA

35. Syrian hamster as an ideal animal model for evaluation of cancer immunotherapy.

Front Immunol

2023 Feb 27

Jia Y, Wang Y, Dunmall LSC

36. The diverse roles of C-type lectin-like receptors in immunity.

Front Immunol

2023 Feb 27

Scur M, Parsons BD, Dey S

37. Transcriptomics and metabolomics analysis reveal the anti-oxidation and immune boosting effects of mulberry leaves in growing mutton sheep.

Front Immunol

2023 Feb 27

Cui X, Yang Y, Zhang M

38. Antimicrobial skin peptides in premature infants: Comparison with term infants and impact of perinatal factors.

Front Immunol

2023 Feb 27

Humberg A, Neuenburg L, Boeckel H

INTRODUCTION: Preterm infants have an immature epidermis barrier function that may lead to an increased permeability to pathogens. On the surface of the human skin, antimicrobial peptides (AMPs) are important molecules of the innate immune system, have broad antimicrobial properties, and provide an essential role in integrity of the microbiome. Given the marked susceptibility of preterm infants to infection, we hypothesize a decreased expression of AMPs on the skin of preterm infants. MATERIALS AND METHODS: In a prospective single-center study with 35 preterm and 20 term infants, we analyzed skin rinsing probes for the presence of the AMPs psoriasin (S100A7) and ribonuclease 7 (RNase 7) via enzyme-linked immunosorbent assay. Samples were taken from preterm infants < 34 0/7 weeks gestational age (mean ± SD gestational age, 28.8 ± 2.4 weeks) on days 0, 7, 14, and 28 after birth. Term infants (> 36 6/7 weeks) (controls) were washed on days 0 and 28. RESULTS: Psoriasin and RNase 7 were both expressed on skin of preterm and term infants and increased in concentration significantly over time. RNase 7 was more expressed in term infants on day 0 [preterm = 1.1 (0.7-2.9) vs. term = 2.0 (1.1-3.4) ng/ml, p = 0.017]. On day 28, premature infants showed higher values of psoriasin [preterm = 10.9 (5.6-14.2) vs. term = 6.3 (3.4-9.0) ng/ml, p < 0.001]. Notably, preterm infants with infectious or inflammatory context driven by histological proof of chorioamnionitis and early-onset or late-onset sepsis had higher concentrations of psoriasin as compared with non-affected preterm infants. After exclusion of infants with inflammatory hit, median concentrations of RNase 7 and psoriasin did not differ between preterm and full-term infants on days 0 and 28. DISCUSSION: Psoriasin and RNase 7 concentrations increase over time on the skin of newborn infants and seem to play a role in the first defense against infection. This is of particularly interest as the role of AMPs on a maturing skin microbiome and its possible new prevention strategies is unclear and needs to be determined.

39. Myeloidcells in the immunosuppressive microenvironment in glioblastoma: The characteristics and therapeutic strategies.

Front Immunol

2023 Feb 27

Huang B, Zhang J, Zong W

40. Characteristics of pathology and transcriptome profiling reveal features of immune response of acutely infected and asymptomatic infected of carp edema virus in Koi.

Front Immunol

2023 Feb 27

Ouyang P, Ren Y, Zhou Y

Koi sleepy disease (KSD) is a high mortality and infection viral disease caused by carp edema virus (CEV), which was a serious threat to aquaculture of common carp and export trade of Koi worldwide. Asymptomatic infection is an important cause of the difficulty in preventing KSD and its worldwide spread, because asymptomatic infection can be activated under appropriate condition. However, the understanding of the molecular correlates of these infections is still unknown. The purpose of this study was to compare the pathology change, enzyme activity, immunoglobulin activity, host and viral gene expression differences in acutely infected and cohabiting asymptomatic Koi infected with CEV. Healthy Koi were used as a control. The gross pathology, histopathology and ultrastructural pathology showed the difference and characteristics damage to the tissues of Koi under different infection conditions. Periodic Acid-Schiff stain (PAS), enzyme activity and immunoglobulin activity revealed changes in the immune response of gill tissue between acutely infected, asymptomatic infected and healthy Koi. A total of 111 and 2484 upregulated genes and 257 and 4940 downregulated genes were founded in healthy Koi vs asymptomatic infected Koi and healthy Koi vs acutely infected Koi, respectively. Additionally, 878 upregulated genes and 1089 downregulated genes were identified in asymptomatic vs. acutely infected Koi. Immune gene categories and their corresponding genes in different comparison groups were revealed. A total of 3, 59 and 28 immune-related genes were identified in the group of healthy Koi vs asymptomatic infected Koi, healthy Koi vs acutely infected Koi and asymptomatic infected Koi vs acutely infected Koi, respectively. Nineteen immune-related genes have the same expression manner both in healthy Koi vs acutely infected Koi and asymptomatic Koi vs acutely infected Koi, while 9 immune-related genes were differentially expressed only in asymptomatic Koi vs acutely infected Koi, which may play a role in viral reactivation. In addition, 8 differentially expressed genes (DEGs) were validated by quantitative reverse transcription PCR (RT-qPCR), and the results were consistent with the RNA-Seq results. In conclusion, the data obtained in this study provide new evidence for further elucidating CEV-host interactions and the CEV infection mechanism and will facilitate the implementation of integrated strategies for controlling CEV infection and spread.

41. Nutrients and rheumatoid arthritis: From the perspective of neutrophils.

Front Immunol

2023 Feb 27

Shao YR, Xu DY, Lin J.

42. Resolvin D1 improves allograft osteointegration and directly enhances osteoblasts differentiation.

Front Immunol

2023 Feb 27

Pinto N, Klein Y, David E

INTRODUCTION: Allografts are the most common bone grafts for repairing osseous defects. However, their use is associated with an increased risk for infections, donor disease transmission and osteointegration deficiency. Resolvin D1 (RvD1) is an endogenous lipid with a scientifically proven pivotal role in inflammation resolution and osteoclastogenesis inhibition. Yet, its biological relevance as a potential bone regenerative drug has been scarcely studied. Here, we aim to investigate the RvD1 effect on allograft osteointegration in the alveolar bone regeneration (ABR) murine model. METHODS: ABR model consisted of osseous defects that were generated by the extraction of the maxillary first molar in C57BL/6 mice. The sockets were filled with allograft and analyzed via RNA sequencing. Then they were locally injected with either RvD1 or saline via single or repeated administrations. The mice were sacrificed 2W after the procedure, and regenerated sites were analyzed using µCT and histology. First, MC3T3-E1 preosteoblasts were plated with IL-17 pro-inflammatory medium, and RANKL/OPG ratio was measured. Secondly, the MC3T3-E1 were cultured w/o RvD1, for 3W. Osteoblasts' markers were evaluated in different days, using qRT-PCR and Alizarin Red staining for calcified matrix. RESULTS: In vivo, neither allograft alone nor single RvD1 administration promote bone regeneration in comparison to the control of spontaneous healing and even triggered an elevation in NR1D1 and IL1RL1 expression, markers associated with inflammation and inhibition of bone cell differentiation. However, repeated RvD1 treatment increased bone content by 135.92% ± 45.98% compared to its specific control, repeated sham, and by 39.12% ± 26.3% when compared to the spontaneous healing control group (n=7/group). Histologically, repeated RvD1 reduced the number of TRAP-positive cells, and enhanced allograft osteointegration with new bone formation. In vitro, RvD1 rescued OPG expression and decreased RANKL/OPG ratio in IL-17 pro-inflammatory conditions. Furthermore, RvD1 increased the expression of RUNX2, OSX, BSP and OC/BGLAP2 and the mineralized extracellular matrix during MC3T3-E1 osteoblasts differentiation. CONCLUSIONS: Repeated administrations of RvD1 promote bone regeneration via a dual mechanism: directly, via enhancement of osteoblasts' differentiation and indirectly, through reduction of osteoclastogenesis and RANKL/OPG ratio. This suggests that RvD1 may be a potential therapeutic bioagent for osseous regeneration following allograft implantation.

43. B cell-activating factor (BAFF) from dendritic cells, monocytes and neutrophils is required for B cell maturation and autoantibody production in SLE-like autoimmune disease.

Front Immunol

2023 Feb 27

Giordano D, Kuley R, Draves KE

PURPOSE AND METHODS: B cell-activating factor (BAFF) contributes to the pathogenesis of autoimmune diseases including systemic lupus erythematosus (SLE). Although several anti-BAFF Abs and derivatives have been developed for the treatment of SLE, the specific sources of BAFF that sustain autoantibody (auto-Ab) producing cells have not been definitively identified. Using BAFF-RFP reporter mice, we identified major changes in BAFF-producing cells in two mouse spontaneous lupus models (Tlr7 Tg mice and Sle1), and in a pristane-induced lupus (PIL) model. RESULTS: First, we confirmed that similar to their wildtype Tlr7 Tg and Sle1 mice counterparts, BAFF-RFP Tlr7 Tg mice and BAFF-RFP Sle1 mice had increased BAFF serum levels, which correlated with increases in plasma cells and auto-Ab production. Next, using the RFP reporter, we defined which cells had dysregulated BAFF production. BAFF-producing neutrophils (Nphs), monocytes (MOs), cDCs, T cells and B cells were all expanded in the spleens of BAFF-RFP Tlr7 Tg mice and BAFF-RFP Sle1 mice compared to controls. Furthermore, Ly6Chi inflammatory MOs and T cells had significantly increased BAFF expression per cell in both spontaneous lupus models, while CD8- DCs up-regulated BAFF expression only in the Tlr7 Tg mice. Similarly, pristane injection of BAFF-RFP mice induced increases in serum BAFF levels, auto-Abs, and the expansion of BAFF-producing Nphs, MOs, and DCs in both the spleen and peritoneal cavity. BAFF expression in MOs and DCs, in contrast to BAFF from Nphs, was required to maintain homeostatic and pristane-induced systemic BAFF levels and to sustain mature B cell pools in spleens and BMs. Although acting through different mechanisms, Nph, MO and DC sources of BAFF were each required for the development of auto-Abs in PIL mice. CONCLUSIONS: Our findings underscore the importance of considering the relative roles of specific myeloid BAFF sources and B cell niches when developing treatments for SLE and other BAFF-associated autoimmune diseases.

44. The STING/TBK1/IRF3/IFN type I pathway is defective in cystic fibrosis.

Front Immunol

2023 Feb 27

Occhigrossi L, Rossin F, Villella VR

45. Identification and investigation of depression-related molecular subtypes in inflammatory bowel disease and the anti-inflammatory mechanisms of paroxetine.

Front Immunol

2023 Feb 27

Ning L, Wang X, Xuan B

46. NFκB signaling in T cell memory.

Front Immunol

2023 Feb 24

Daniels MA, Luera D, Teixeiro E.

47. Single-cell transcriptomic analysis in two patients with rare systemic autoinflammatory diseases treated with anti-TNF therapy.

Front Immunol

2023 Feb 24

Hua Y, Wu N, Miao J

48. The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

Front Immunol

2023 Feb 24

Chen H, Huang X, Zeng C

BACKGROUND: The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association. METHODS: According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay. RESULTS: Fifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014). CONCLUSIONS: Our findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

49. Giant phagocytes (Gφ) and neutrophil-macrophage hybrids in human carotid atherosclerotic plaques - An activated phenotype.

Front Immunol

2023 Feb 24

Lavie L, Si-On E, Hoffman A.

INTRODUCTION: A small subpopulation of CD66b+ neutrophils with extended lifespan and immensely large size was identified in vitro. They internalized dead neutrophil remnants and cellular debris, transforming them into giant phagocytes (Gφ) resembling macrophage-foam cells with a massive lipid content and CD68+ scavenger receptor expression. Thus, we sought to investigate if similar CD66b+ neutrophils with altered morphology and functions exist in inflammatory/atherosclerotic conditions in vivo, by using human carotid atherosclerotic plaques. METHODS: Thirty-three plaques were obtained from 31 patients undergoing endarterectomy. Carotid plaques were analyzed for CD markers by immunohistochemistry and immunofluorescence and quantitatively analyzed by confocal microscopy. Intra-plaque lipids were stained with Oil Red O. RESULTS: Plaque CD66b+ neutrophils co-expressed myeloperoxidase (MPO)+ and neutrophil elastase (NE)+. Also, co-expression of CD66b+/CD68+, CD66b+/CD36+, CD66b+/vascular-endothelial-growth- factor (VEGF)+ and 3-nitrotyrosine (3-NT)+/NE+ was noted. Similarly, macrophages co-expressed CD163+/CD68+, CD163+/VEGF+ and CD163+/3-NT+. Both cell types were predominantly localized in lipid-rich areas and stained for lipids. CD66b+ and CD163+ expressions were highly positively correlated with each other and each with CD68+, and 3-NT+. Morphologically, CD66+ cells were big, had a rounded nucleus, and resembled macrophage-foam cell morphology as well as that of Gφ in vitro. To clarify whether CD66b+ and CD163+ cells represent two distinct plaque-populations, plaques were double-stained for CD66b/CD163 co-localization. A third of the plaques was negative for CD66b/CD163 co-localization. Other plaques had a low co-localization, but in few plaques, co-localization was high, collectively, indicating that in some of plaques there were two distinct cell populations, those resembling Gφ, and those co-expressing CD66b+/CD163+, demonstrating a hybrid neutrophil-macrophage phenotype. Interestingly, CD66b+/CD163+ co-localization was highly positively correlated with the oxidant 3-NT, hence, supporting trans-differentiation of CD66b+ cells to CD163+ Cells. Conversely, phagocytosis of dead neutrophils by macrophages might have also occurred. DISCUSSION: Thus, we conclude that in some of the plaques CD66b+ cells might represent cells resembling Gφ that developed in prolonged culture conditions. Yet, CD66b+/CD163+ co-expressing cells represent a new neutrophil-macrophage hybrid population of unknown transitioning point, possibly by adopting macrophage markers or contrariwise. Nonetheless, the significance and functions of these cells in plaque biology or other inflammatory/atherosclerotic conditions should be unveiled.

50. Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry.

Front Immunol

2023 Feb 24

Busca A, Salmanton-García J, Marchesi F

51. Novel regulatory role of non-coding RNAs in ankylosing spondylitis.

Front Immunol

2023 Feb 24

Fang Y, Liu J.

52. Single-cell analysis reveals TLR-induced macrophage heterogeneity and quorum sensing dictate population wide anti-inflammatory feedback in response to LPS.

Front Immunol

2023 Feb 24

Tiemeijer BM, Heester S, Sturtewagen AYW

53. Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges.

Front Immunol

2023 Feb 24

Xia Y, Zhu J, Yang R

54. A meta-analysis of chemokines in vitiligo: Recruiting immune cells towards melanocytes.

Front Immunol

2023 Feb 24

Speeckaert R, Belpaire A, Speeckaert MM

55. Cross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and old.

Front Immunol

2023 Feb 24

Clark F, Gil A, Thapa I

Older people have difficulty controlling infection with common viruses such as influenza A virus (IAV), RNA virus which causes recurrent infections due to a high rate of genetic mutation, and Epstein Barr virus (EBV), DNA virus which persists in B cells for life in the 95% of people that become acutely infected. We questioned whether changes in epitope-specific memory CD8 T cell receptor (TCR) repertoires to these two common viruses could occur with increasing age and contribute to waning immunity. We compared CD8 memory TCR alpha and beta repertoires in two HLA-A2+ EBV- and IAV-immune donors, young (Y) and older (O) donors to three immunodominant epitopes known to be cross-reactive, IAV-M158-66 (IAV-M1), EBV-BMLF1280-288 (EBV-BM), and EBV-BRLF1109-117 (EBV-BR). We, therefore, also designed these studies to examine if TCR cross-reactivity could contribute to changes in repertoire with increasing age. TCR high throughput sequencing showed a significant difference in the pattern of TRBV usage between Y and O. However, there were many more differences in AV and AJ usage, between the age groups suggesting that changes in TCRα usage may play a greater role in evolution of the TCR repertoire emphasizing the importance of studying TRAV repertoires. With increasing age there was a preferential retention of TCR for all three epitopes with features in their complementarity-determining region (CDR3) that increased their ease of generation, and their cross-reactive potential. Young and older donors differed in the patterns of AV/AJ and BV/BJ pairings and usage of dominant CDR3 motifs specific to all three epitopes. Both young and older donors had cross-reactive responses between these 3 epitopes, which were unique and differed from the cognate responses having features that suggested they could interact with either ligand. There was an increased tendency for the classic IAV-M1 specific clone BV19-IRSS-JB2.7/AV27-CAGGGSQGNLIF-AJ42 to appear among the cross-reactive clones, suggesting that the dominance of this clone may relate to its cross-reactivity with EBV. These results suggest that although young and older donors retain classic TCR features for each epitope their repertoires are gradually changing with age, maintaining TCRs that are cross-reactive between these two common human viruses, one with recurrent infections and the other a persistent virus which frequently reactivates.

56. Highly purified and functionally stable in vitro expanded allospecific Tr1 cells expressing immunosuppressive graft-homing receptors as new candidates for cell therapy in solid organ transplantation.

Front Immunol

2023 Feb 24

Arteaga-Cruz S, Cortés-Hernández A, Alvarez-Salazar EK

The development of new strategies based on the use of Tr1 cells has taken relevance to induce long-term tolerance, especially in the context of allogeneic stem cell transplantation. Although Tr1 cells are currently identified by the co-expression of CD49b and LAG-3 and high production of interleukin 10 (IL-10), recent studies have shown the need for a more exhaustive characterization, including co-inhibitory and chemokines receptors expression, to ensure bona fide Tr1 cells to be used as cell therapy in solid organ transplantation. Moreover, the proinflammatory environment induced by the allograft could affect the suppressive function of Treg cells, therefore stability of Tr1 cells needs to be further investigated. Here, we establish a new protocol that allows long-term in vitro expansion of highly purified expanded allospecific Tr1 (Exp-allo Tr1). Our expanded Tr1 cell population becomes highly enriched in IL-10 producers (> 90%) and maintains high expression of CD49b and LAG-3, as well as the co-inhibitory receptors PD-1, CTLA-4, TIM-3, TIGIT and CD39. Most importantly, high dimensional analysis of Exp-allo Tr1 demonstrated a specific expression profile that distinguishes them from activated conventional T cells (T conv), showing overexpression of IL-10, CD39, CTLA-4 and LAG-3. On the other hand, Exp-allo Tr1 expressed a chemokine receptor profile relevant for allograft homing and tolerance induction including CCR2, CCR4, CCR5 and CXCR3, but lower levels of CCR7. Interestingly, Exp-allo Tr1 efficiently suppressed allospecific but not third-party T cell responses even after being expanded in the presence of proinflammatory cytokines for two extra weeks, supporting their functional stability. In summary, we demonstrate for the first time that highly purified allospecific Tr1 (Allo Tr1) cells can be efficiently expanded maintaining a stable phenotype and suppressive function with homing potential to the allograft, so they may be considered as promising therapeutic tools for solid organ transplantation.

57. New-age vaccine adjuvants, their development, and future perspective.

Front Immunol

2023 Feb 24

Verma SK, Mahajan P, Singh NK

58. Characteristic gene expression in the liver monocyte-macrophage-DC system is associated with the progression of fibrosis in NASH.

Front Immunol

2023 Feb 24

Wang X, Wang Z, Liu B

59. Meteorin-like/Metrnl, a novel secreted protein implicated in inflammation, immunology, and metabolism: A comprehensive review of preclinical and clinical studies.

Front Immunol

2023 Feb 24

Li Z, Gao Z, Sun T

60. Unisexual infection with Schistosoma mansoni in mice has the potential to boost the immune response against eggs after challenge infection.

Front Immunol

2023 Feb 24

Reinholdt C, Winkelmann F, Koslowski N

INTRODUCTION: The complexity of the Schistosoma spp. life cycle and their effective immune evasion strategies, makes vaccine development challenging. Unisexual infection models, that excludes any immunomodulatory effects of the parasite eggs, may contribute to a better understanding of complex immunological processes and identification of new targets for vaccine research. We have recently shown that long-term unisexual infection with schistosomes in mice results in an unpolarized Th1/Th2 response associated with an abnormally enlarged spleen and diffuse liver inflammation. Herein, we investigated whether (i) unisexual worms can mate after three months of single sex infection and (ii) thus the Th2 response induced by oviposition can reverse or heal the described systemic inflammation. METHODS: Therefore, we infected 6-8 weeks old female C57BL/6j mice with 100 male or female cercariae and reinfected with the opposite sex for the same period after 12 weeks. At 24 weeks after initial infection, we histologically examined worm mating, as evidenced by the presence of parasite eggs, infection-related pathology associated with eggs, and characterization of fibrosis in the livers. RESULTS: Single worms are able to mate months after unisexual infection and start oviposition. Egg deposition has been associated with a typical Th2 immune response in the liver after unisexual reinfection, accompanied by increased recruitment of CD4+ T cells. Hepatic collagen levels were significantly increased in the reinfected groups compared to the naive and unisexually infected group. DISCUSSION: Our results indicate that the eggs are able to restore the Th1/Th2 immune balance of a previous unisexual infection. However, the organ damage caused by the unisexual worms does not subside, but rather provides the baseline for the emerging egg-triggered inflammation and fibrosis. Since single schistosomes can mate even several weeks after unisexual infection and then accumulate worm- and egg-related organ damage, infection status without positive egg detection is very important, especially in areas with low prevalence.

61. Identification of tumor mutation burden-associated molecular and clinical features in cancer by analyzing multi-omics data.

Front Immunol

2023 Feb 24

Li M, Gao X, Wang X.

BACKGROUND: Tumor mutation burden (TMB) has been recognized as a predictive biomarker for immunotherapy response in cancer. Systematic identification of molecular features correlated with TMB is significant, although such investigation remains insufficient. METHODS: We analyzed associations of somatic mutations, pathways, protein expression, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), competing endogenous RNA (ceRNA) antitumor immune signatures, and clinical features with TMB in various cancers using multi-omics datasets from The Cancer Genome Atlas (TCGA) program and datasets for cancer cohorts receiving the immune checkpoint blockade therapy. RESULTS: Among the 32 TCGA cancer types, melanoma harbored the highest percentage of high-TMB (≥ 10/Mb) cancers (49.4%), followed by lung adenocarcinoma (36.9%) and lung squamous cell carcinoma (28.1%). Three hundred seventy-six genes had significant correlations of their mutations with increased TMB in various cancers, including 11 genes (ARID1A, ARID1B, BRIP1, NOTCH2, NOTCH4, EPHA5, ROS1, FAT1, SPEN, NSD1,and PTPRT) with the characteristic of their mutations associated with a favorable response to immunotherapy. Based on the mutation profiles in three genes (ROS1, SPEN, and PTPRT), we defined the TMB prognostic score that could predict cancer survival prognosis in the immunotherapy setting but not in the non-immunotherapy setting. It suggests that the TMB prognostic score's ability to predict cancer prognosis is associated with the positive correlation between immunotherapy response and TMB. Nine cancer-associated pathways correlated positively with TMB in various cancers, including nucleotide excision repair, DNA replication, homologous recombination, base excision repair, mismatch repair, cell cycle, spliceosome, proteasome, and RNA degradation. In contrast, seven pathways correlated inversely with TMB in multiple cancers, including Wnt, Hedgehog, PI3K-AKT, MAPK, neurotrophin, axon guidance, and pathways in cancer. High-TMB cancers displayed higher levels of antitumor immune signatures and PD-L1 expression than low-TMB cancers in diverse cancers. The association between TMB and survival prognosis was positive in bladder, gastric, and endometrial cancers and negative in liver and head and neck cancers. TMB also showed significant associations with age, gender, height, weight, smoking, and race in certain cohorts. CONCLUSIONS: The molecular and clinical features significantly associated with TMB could be valuable predictors for TMB and immunotherapy response and therefore have potential clinical values for cancer management.

62. Comprehensive protocols for culturing and molecular biological analysis of IBD patient-derived colon epithelial organoids.

Front Immunol

2023 Feb 23

Gopalakrishnan S, Bakke I, Hansen MD

63. The adenosinergic machinery in cancer: In-tandem insights from basic mechanisms to therapy.

Front Immunol

2023 Feb 23

Kang C, Liu L, Wu C

64. NLRP6 deficiency expands a novel CD103(+) B cell population that confers immune tolerance in NOD mice.

Front Immunol

2023 Feb 23

Pearson JA, Peng J, Huang J

65. The NLRP1 inflammasome in skin diseases.

Front Immunol

2023 Feb 23

Burian M, Schmidt MF, Yazdi AS.

66. Imaging assessment of toxicity related to immune checkpoint inhibitors.

Front Immunol

2023 Feb 23

Berz AM, Boughdad S, Vietti-Violi N

In recent years, a wide range of cancer immunotherapies have been developed and have become increasingly important in cancer treatment across multiple oncologic diseases. In particular, immune checkpoint inhibitors (ICIs) offer promising options to improve patient outcomes. However, a major limitation of these treatments consists in the development of immune-related adverse events (irAEs) occurring in potentially any organ system and affecting up to 76% of the patients. The most frequent toxicities involve the skin, gastrointestinal tract, and endocrine system. Although mostly manageable, potentially life-threatening events, particularly due to neuro-, cardiac, and pulmonary toxicity, occur in up to 30% and 55% of the patients treated with ICI-monotherapy or -combination therapy, respectively. Imaging, in particular computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT), plays an important role in the detection and characterization of these irAEs. In some patients, irAEs can even be detected on imaging before the onset of clinical symptoms. In this context, it is particularly important to distinguish irAEs from true disease progression and specific immunotherapy related response patterns, such as pseudoprogression. In addition, there are irAEs which might be easily confused with other pathologies such as infection or metastasis. However, many imaging findings, such as in immune-related pneumonitis, are nonspecific. Thus, accurate diagnosis may be delayed underling the importance for adequate imaging features characterization in the appropriate clinical setting in order to provide timely and efficient patient management. 18F-FDG-PET/CT and radiomics have demonstrated to reliably detect these toxicities and potentially have predictive value for identifying patients at risk of developing irAEs. The purpose of this article is to provide a review of the main immunotherapy-related toxicities and discuss their characteristics on imaging.

67. MAIT cells and the microbiome.

Front Immunol

2023 Feb 23

Jabeen MF, Hinks TSC.

Mucosal associated invariant T (MAIT) cells are innate-like T lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant αβ T cell receptor (TCR) recognizing microbial derived intermediates of riboflavin synthesis presented by the MHC-Ib molecule MR1. At barrier sites MAIT cells occupy a prime position for interaction with commensal microorganisms, comprising the microbiota. The microbiota is a rich source of riboflavin derived antigens required in early life to promote intra-thymic MAIT cell development and sustain a life-long population of tissue resident cells. A symbiotic relationship is thought to be maintained in health whereby microbes promote maturation and homeostasis, and in turn MAIT cells can engage a TCR-dependent "tissue repair" program in the presence of commensal organisms conducive to sustaining barrier function and integrity of the microbial community. MAIT cell activation can be induced in a MR1-TCR dependent manner or through MR1-TCR independent mechanisms via pro-inflammatory cytokines interleukin (IL)-12/-15/-18 and type I interferon. MAIT cells provide immunity against bacterial, fungal and viral pathogens. However, MAIT cells may have deleterious effects through insufficient or exacerbated effector activity and have been implicated in autoimmune, inflammatory and allergic conditions in which microbial dysbiosis is a shared feature. In this review we summarize the current knowledge on the role of the microbiota in the development and maintenance of circulating and tissue resident MAIT cells. We also explore how microbial dysbiosis, alongside changes in intestinal permeability and imbalance between pro- and anti-inflammatory components of the immune response are together involved in the potential pathogenicity of MAIT cells. Whilst there have been significant improvements in our understanding of how the microbiota shapes MAIT cell function, human data are relatively lacking, and it remains unknown if MAIT cells can conversely influence the composition of the microbiota. We speculate whether, in a human population, differences in microbiomes might account for the heterogeneity observed in MAIT cell frequency across mucosal sites or between individuals, and response to therapies targeting T cells. Moreover, we speculate whether manipulation of the microbiota, or harnessing MAIT cell ligands within the gut or disease-specific sites could offer novel therapeutic strategies.

68. Orally administered Lactiplantibacillus plantarum OLL2712 decreased intestinal permeability, especially in the ileum: Ingested lactic acid bacteria alleviated obesity-induced inflammation by collaborating with gut microbiota.

Front Immunol

2023 Feb 23

Wang Y, Takano T, Zhou Y

INTRODUCTION: Chronic inflammation caused by dietary obesity has been considered to induce lifestyle-related diseases and functional ingredients with anti-inflammatory effects are attracting attention. Although multiple studies on obesity had proved the anti-inflammatory effects of ingestion of lactic acid bacteria (LAB) and other functional ingredients on adipose tissue, the precise effects on the intestine, especially on the individual intestinal segments have not been made clear. In this study, we elucidated the mechanisms of Lactiplantibacillus plantarum (basonym: Lactobacillus plantarum) OLL2712 in suppressing obesity-induced inflammation using high fat diet (HFD)-fed mice obesity model. METHODS: We orally administered heat-treated LAB to HFD-fed mice model, and investigated the inflammatory changes in adipose tissue and intestinal immune cells. We also analyzed gut microbiota, and evaluated the inflammation and permeability of the duodenum, jejunum, ileum and colon; four intestinal segments differing in gut bacteria composition and immune response. RESULTS: After 3-week LAB administration, the gene expression levels of proinflammatory cytokines were downregulated in adipose tissue, colon, and Peyer's patches (PP)-derived F4/80+ cells. The LAB treatment alleviated obesity-related gut microbiota imbalance. L. plantarum OLL2712 treatment helps maintain intestinal barrier function, especially in the ileum, possibly by preventing ZO-1 and Occludin downregulation. DISCUSSION: Our results suggest that the oral administration of the LAB strain regulated the gut microbiota, suppressed intestinal inflammation, and improved the gut barrier, which could inhibit the products of obesity-induced gut dysbiosis from translocating into the bloodstream and the adipose tissue, through which the LAB finally alleviated the inflammation caused by dietary obesity. Barrier improvement was observed, especially in the ileum, suggesting collaborative modulation of the intestinal immune responses by ingested LAB and microbiota.

69. The effect of sodium thiosulfate on immune cell metabolism during porcine hemorrhage and resuscitation.

Front Immunol

2023 Feb 23

Wolfschmitt EM, Hogg M, Vogt JA

INTRODUCTION: Sodium thiosulfate (Na2S2O3), an H2S releasing agent, was shown to be organ-protective in experimental hemorrhage. Systemic inflammation activates immune cells, which in turn show cell type-specific metabolic plasticity with modifications of mitochondrial respiratory activity. Since H2S can dose-dependently stimulate or inhibit mitochondrial respiration, we investigated the effect of Na2S2O3 on immune cell metabolism in a blinded, randomized, controlled, long-term, porcine model of hemorrhage and resuscitation. For this purpose, we developed a Bayesian sampling-based model for 13C isotope metabolic flux analysis (MFA) utilizing 1,2-13C2-labeled glucose, 13C6-labeled glucose, and 13C5-labeled glutamine tracers. METHODS: After 3 h of hemorrhage, anesthetized and surgically instrumented swine underwent resuscitation up to a maximum of 68 h. At 2 h of shock, animals randomly received vehicle or Na2S2O3 (25 mg/kg/h for 2 h, thereafter 100 mg/kg/h until 24 h after shock). At three time points (prior to shock, 24 h post shock and 64 h post shock) peripheral blood mononuclear cells (PBMCs) and granulocytes were isolated from whole blood, and cells were investigated regarding mitochondrial oxygen consumption (high resolution respirometry), reactive oxygen species production (electron spin resonance) and fluxes within the metabolic network (stable isotope-based MFA). RESULTS: PBMCs showed significantly higher mitochondrial O2 uptake and lower O2•- production in comparison to granulocytes. We found that in response to Na2S2O3 administration, PBMCs but not granulocytes had an increased mitochondrial oxygen consumption combined with a transient reduction of the citrate synthase flux and an increase of acetyl-CoA channeled into other compartments, e.g., for lipid biogenesis. CONCLUSION: In a porcine model of hemorrhage and resuscitation, Na2S2O3 administration led to increased mitochondrial oxygen consumption combined with stimulation of lipid biogenesis in PBMCs. In contrast, granulocytes remained unaffected. Granulocytes, on the other hand, remained unaffected. O2•- concentration in whole blood remained constant during shock and resuscitation, indicating a sufficient anti-oxidative capacity. Overall, our MFA model seems to be is a promising approach for investigating immunometabolism; especially when combined with complementary methods.

70. NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells.

Front Immunol

2023 Feb 23

Mussbacher M, Derler M, Basílio J

71. Canine peripheral blood TCRαβ T cell atlas: Identification of diverse subsets including CD8A(+) MAIT-like cells by combined single-cell transcriptome and V(D)J repertoire analysis.

Front Immunol

2023 Feb 23

Eschke M, Moore PF, Chang H

72. Ninety-six-hour starved peripheral blood mononuclear cell supernatant inhibited LA7 breast cancer stem cells induced tumor via reduction in angiogenesis and alternations in Gch1 and Spr expressions.

Front Immunol

2023 Feb 23

Mehri M, Gheitasi R, Pourbagher R

INTRODUCTION: The microenvironment of solid tumors such as breast cancer is heterogeneous and complex, containing different types of cell, namely, cancer stem cells and immune cells. We previously reported the immunoregulatory behavior of the human immune cell in a solid tumor microenvironment-like culture under serum starvation stress for 96 h. Here, we examined the effect of this culture-derived solution on breast cancer development in rats. METHOD: Ninety-six-hour starved PBMCs supernatant (96 h-SPS) was collected after culturing human PBMCs for 96 h under serum starvation condition. Breast cancer stem cells, LA7 cell line, was used for in vitro study by analyzing gene expression status and performing cytotoxicity, proliferation, scratch wound healing assays, followed by in vivo tumor induction in three groups of mature female Sprague Dawley rats. Animals were treated with 96 h-SPS or RPMI and normal saline as control, n = 6 for each group. After biochemical analysis of iron, lactate, and pH levels in the dissected tumors, Ki67 antigen expression, angiogenesis, and necrosis evaluation were carried out. Metabolic-related gene expression was assessed using RT-qPCR. Moreover, 96 h-SPS composition was discovered by Nano-LC-ESI-MS/MS. RESULTS: 96 h-SPS solution reduced the LA7 cell viability, proliferation, and migration and Gch1 and Spr genes expression in vitro (p< 0.05), whereas stemness gene Oct4 was upregulated (p< 0.01). The intracellular lactate was significantly decreased in the 96 h-SPS treated group (p = 0.007). In this group, Gch1 and Spr were significantly downregulated (p< 0.05), whereas the Sox2 and Oct4 expression was not changed significantly. The number of vessels and mitosis (Ki67+ cells) in the 96 h-SPS-treated group was significantly reduced (p = 0.024). The increased rate of necrosis in this group was statistically significant (p = 0.04). Last, proteomics analysis revealed candidate effectors' components of 96 h-SPS solution. CONCLUSION: 96 h-SPS solution may help to prevent cancer stem cell mediated tumor development. This phenomenon could be mediated through direct cytotoxic effects, inhibition of cell proliferation and migration in association with reduction in Gch1 and Spr genes expression, angiogenesis and mitosis rate, and necrosis augmentation. The preliminary data obtained from the present study need to be investigated on a larger scale and can be used as a pilot for further studies on the biology of cancer development.

73. Galectins can serve as biomarkers in COVID-19: A comprehensive systematic review and meta-analysis.

Front Immunol

2023 Feb 23

Behnoush AH, Khalaji A, Alemohammad SY

74. Unmet needs in ANCA-associated vasculitis: Physicians' and patients' perspectives.

Front Immunol

2023 Feb 23

Quartuccio L, Treppo E, Urso L

75. Targeting regulatory T cells for cardiovascular diseases.

Front Immunol

2023 Feb 23

Wang X, Zhou H, Liu Q

76. Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants.

Front Immunol

2023 Feb 23

Carnell GW, Billmeier M, Vishwanath S

77. Case report: Immune profiling links neutrophil and plasmablast dysregulation to microvascular damage in post-COVID-19 Multisystem Inflammatory Syndrome in Adults (MIS-A).

Front Immunol

2023 Feb 23

Gillrie MR, Rosin N, Sinha S

78. Genetic polymorphisms in immune- and inflammation-associated genes and their association with bovine mastitis resistance/susceptibility.

Front Immunol

2023 Feb 23

Khan MZ, Wang J, Ma Y

79. LINC01798/miR-17-5p axis regulates ITGA8 and causes changes in tumor microenvironment and stemness in lung adenocarcinoma.

Front Immunol

2023 Feb 23

Li X, Zhu G, Li Y

80. Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination.

Front Immunol

2023 Feb 23

Ishikawa M, Shimada Y, Ozono T

81. Bruton's tyrosine kinase inhibition attenuates disease progression by reducing renal immune cell invasion in mice with hemolytic-uremic syndrome.

Front Immunol

2023 Feb 23

Kröller S, Wissuwa B, Dennhardt S

82. Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis.

Front Immunol

2023 Feb 23

Wang L, Wei Z, Pan F

83. Understanding fibroblast-immune cell interactions via co-culture models and their role in asthma pathogenesis.

Front Immunol

2023 Feb 23

Thiam F, Yazeedi SA, Feng K

84. Development and validation of a rapid and easy-to-perform point-of-care lateral flow immunoassay (LFIA) for the detection of SARS-CoV-2 spike protein.

Front Immunol

2023 Feb 23

Mohammad S, Wang Y, Cordero J

Development and validation of rapid and easy-to-perform diagnostics continue to be a high priority during the current COVID-19 pandemic. Although vaccines are now widely available, early detection and consistent transmission control provide ideal means to mitigate the spread of SARS-CoV-2. Nucleic acid-based real-time PCR tests are widely acknowledged as the gold standard for reliable diagnosis of COVID-19 infection. These tests are based on detecting viable or nonviable viral nucleic acids. SARS-CoV-2 spike protein is an alternative and ideal target for SARS-CoV-2 diagnosis in the early phase of infection, but point-of-care kits to detect the SARS-CoV-2 spike protein are limited. Here we describe a rapid and convenient method based on Lateral Flow Immunoassay (LFIA) to detect SARS-CoV-2 spike proteins, including SARS-CoV-2 variants (A.23.1, B.1.1.1, 1.617.2, B.1.1.7, B.1.351, P.1, N501Y, R.1, P681H, P3, UK, and South African) within 5 to 10 minutes. We generated highly specific monoclonal antibodies (mAbs) against rationally designed SARS-CoV-2 spike protein. Matched pair mAbs were selected by epitope mapping and employed as antigen capture reagents by spotting onto a nitrocellulose membrane and as detector reagents by conjugation with colloidal gold nanoparticles. We evaluated the performance of the LFIA using recombinant spike proteins of SARS-CoV-2 and several SARS-CoV-2 variants. The specificity of the LFIA was assessed using heat-inactivated SARS-CoV-2 and related human coronaviruses (HCoV-OC43, HCoV-229E, HCoV-HKU1, and HCoV-NL63) and an FDA-approved respiratory pathogens (RP) panel. The assay exhibited 98% specificity and acceptable performance with respect to the minimum limit of detection (25 ng/test) in validation tests. This new LFIA provides improved performance for the early diagnosis of SARS-CoV-2, particularly for home monitoring and in situations with limited access to molecular methods.

85. Alpha fetoprotein promotes polarization of macrophages towards M2-like phenotype and inhibits macrophages to phagocytize hepatoma cells.

Front Immunol

2023 Feb 23

Zhang M, Liu K, Zhang Q

86. Dysregulated low-density granulocyte contributes to early spontaneous abortion.

Front Immunol

2023 Feb 23

Ye H, Li L, Dong Y

Spontaneous abortion (SA) is a common adverse pregnancy event with unclarified pathogenesis and limited therapeutic efficiency. Although most SA cases with the euploid embryo(s) are associated with immunological factors, the contribution of low-density granulocyte (LDG) in SA pathogenesis is rarely reported. This study aimed to investigate the serial characteristics and possible contribution of LDG and their subpopulations in early pregnancy, especially in early SA. Unpregnant (UP), normally pregnant (NP), and SA women were recruited, and the peripheral blood and endometrium/decidua were collected for LDG isolation and histological observation. The percentage, phenotype, and subpopulations of LDG were analyzed via flow cytometric analysis, and the ability of Nets formation was assessed by immunofluorescent and immunohistochemical assays. As a result, 43 participants were enrolled, including 10 UP, 15 NP, and 18 SA women. Compared with the UP group, the LDG percentage in peripheral blood mononuclear cells (PBMCs) and decidual immune cells (DICs) increased in the NP group, while the loss of this increase was observed in the SA group. Meanwhile, CD16int/- cell percentage in peripheral blood LDG (PB-LDG) increased in the NP and SA groups, and insufficient activation of CD16hi PB-LDG characterized by reduced CD11b expression was discovered in the SA group. Moreover, the LDG percentage in DICs was higher than that in PBMCs, and the decidual LDG (D-LDG) showed a surface marker expression profile that is easier to be activated in the pregnant cohort (NP + SA women). Finally, increased decidual Nets formation was observed in the SA group compared with the NP group, and more Nets formation was detected in D-LDG of NP and SA women following PMA stimulation. Overall, LDG participates in the maintenance of early pregnancy, while dysregulated LDG is responsible for early SA, providing novel potential targets for further exploration of SA pathogenesis and therapeutics.

87. Potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression based on bioinformatics analysis.

Front Immunol

2023 Feb 23

Zhou TT, Sun JJ, Tang LD

BACKGROUND: Rheumatoid arthritis (RA) and depression are prevalent diseases that have a negative impact on the quality of life and place a significant economic burden on society. There is increasing evidence that the two diseases are closely related, which could make the disease outcomes worse. In this study, we aimed to identify diagnostic markers and analyzed the therapeutic potential of key genes. METHODS: We assessed the differentially expressed genes (DEGs) specific for RA and Major depressive disorder (MDD) and used weighted gene co-expression network analysis (WGCNA) to identify co-expressed gene modules by obtaining the Gene expression profile data from Gene Expression Omnibus (GEO) database. By using the STRING database, a protein-protein interaction (PPI) network constructed and identified key genes. We also employed two types of machine learning techniques to derive diagnostic markers, which were assessed for their association with immune cells and potential therapeutic effects. Molecular docking and in vitro experiments were used to validate these analytical results. RESULTS: In total, 48 DEGs were identified in RA with comorbid MDD. The PPI network was combined with WGCNA to identify 26 key genes of RA with comorbid MDD. Machine learning-based methods indicated that RA combined with MDD is likely related to six diagnostic markers: AURKA, BTN3A2, CXCL10, ERAP2, MARCO, and PLA2G7. CXCL10 and MARCO are closely associated with diverse immune cells in RA. However, apart from PLA2G7, the expression levels of the other five genes were associated with the composition of the majority of immune cells in MDD. Molecular docking and in vitro studies have revealed that Aucubin (AU) exerts the therapeutic effect through the downregulation of CXCL10 and BTN3A2 gene expression in PC12 cells. CONCLUSION: Our study indicates that six diagnostic markers were the basis of the comorbidity mechanism of RA and MDD and may also be potential therapeutic targets. Further mechanistic studies of the pathogenesis and treatment of RA and MDD may be able to identify new targets using these shared pathways.

88. Engineered antibody cytokine chimera synergizes with DNA-launched nanoparticle vaccines to potentiate melanoma suppression in vivo.

Front Immunol

2023 Feb 23

Tursi NJ, Xu Z, Helble M

89. Prognostic model for predicting outcome and guiding treatment decision for unresectable hepatocellular carcinoma treated with lenvatinib monotherapy or lenvatinib plus immunotherapy.

Front Immunol

2023 Feb 23

Guo DZ, Zhang SY, Dong SY

BACKGROUND: Lenvatinib monotherapy and combination therapy with immune checkpoint inhibitors (ICI) were widely applied for unresectable hepatocellular carcinoma (uHCC). However, many patients failed to benefit from the treatments. A prognostic model was needed to predict the treatment outcomes and guide clinical decisions. METHODS: 304 patients receiving lenvatinib monotherapy or lenvatinib plus ICI for uHCC were retrospectively included. The risk factors derived from the multivariate analysis were used to construct the predictive model. The C-index and area under the receiver-operating characteristic curve (AUC) were calculated to assess the predictive efficiency. RESULTS: Multivariate analysis revealed that protein induced by vitamin K absence or antagonist-II (PIVKA-II) (HR, 2.05; P=0.001) and metastasis (HR, 2.07; P<0.001) were independent risk factors of overall survival (OS) in the training cohort. Herein, we constructed a prognostic model called PIMET score and stratified patients into the PIMET-low group (without metastasis and PIVKA-II<600 mAU/mL), PIMET-int group (with metastasis or PIVKA-II>600 mAU/mL) and PIMET-high group (with metastasis and PIVKA-II>600 mAU/mL). The C-index of PIMET score for the survival prediction was 0.63 and 0.67 in the training and validation cohort, respectively. In the training cohort, the AUC of 12-, 18-, and 24-month OS was 0.661, 0.682, and 0.744, respectively. The prognostic performances of the model were subsequently validated. The AUC of 12-, 18-, and 24-month OS was 0.724, 0.726, and 0.762 in the validation cohort. Subgroup analyses showed consistent predictive value for patients receiving lenvatinib monotherapy and patients receiving lenvatinib plus ICI. The PIMET score could also distinguish patients with different treatment responses. Notably, the combination of lenvatinib and ICI conferred survival benefits to patients with PIMET-int or PIMET-high, instead of patients with PIMET-low. CONCLUSION: The PIMET score comprising metastasis and PIVKA-II could serve as a helpful prognostic model for uHCC receiving lenvatinib monotherapy or lenvatinib plus ICI. The PIMET score could guide the treatment decision and facilitate precision medicine for uHCC patients.

90. B cell receptor repertoire analysis from autopsy samples of COVID-19 patients.

Front Immunol

2023 Feb 23

Iwabuchi S, Tsukahara T, Okayama T

91. Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer.

Front Immunol

2023 Feb 23

Xu Y, Xia Z, Sun X

BACKGROUND: Bladder cancer is the most common malignancy of the urinary system. However, patient prognosis and treatment outcomes in bladder cancer are difficult to predict owing to high tumor heterogeneity. Given that abnormal glutamine metabolism has been identified as a key factor driving the progression of bladder cancer, it is necessary to assess the prognosis and therapeutic efficacy of bladder cancer treatments based on an analysis of glutamine metabolism-related genes. METHODS: We used bladder cancer sample data downloaded from The Cancer Genome Atlas to identify glutamine metabolism-related genes as prognostic markers, and established a novel Glutamine Metabolism Immunity Index (GMII) based on univariate and multivariate COX regression analyses. On the basis of GMII values, bladder cancer patients were divided into high- and low-risk groups, and systematic analysis was conducted for clinical features, somatic mutations, immune cell infiltration, chemotherapeutic response, and immunotherapeutic efficacy. Candidate small-molecule drugs targeting the GMII core target proteins were identified based on molecular docking analysis. RESULTS: The GMII consisting of eight independent prognostic genes was established to be an excellent tool for predicting the survival in patients with bladder cancer and was validated using multiple datasets. Compared with patients in the high-risk group, those in the low-risk group had significantly better responses to gemcitabine and immune checkpoint blockade. In addition, we predicted 12 potential small-molecule drugs that could bind to three of the GMII core target proteins. CONCLUSIONS: The GMII can be used to accurately predict the prognosis and immunotherapeutic response of bladder cancer patients, as well as candidate small-molecule drugs. Furthermore, the novel "Glutamine Metabolism-related Gene"-guided strategy for predicting survival and chemo-immunotherapeutic efficacy may also be applicable for cancers other than bladder cancer.

92. Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization.

Front Immunol

2023 Feb 23

Zhou X, Chen H, Shi Y

BACKGROUND: Peritoneal dialysis (PD) is an effective replacement therapy for end-stage renal disease patients. However, long-term exposure to peritoneal dialysate will lead to the development of peritoneal fibrosis. Epigenetics has been shown to play an important role in peritoneal fibrosis, but the role of histone deacetylases 8 (HDAC8) in peritoneal fibrosis have not been elucidated. In this research, we focused on the role and mechanisms of HDAC8 in peritoneal fibrosis and discussed the mechanisms involved. METHODS: We examined the expression of HDAC8 in the peritoneum and dialysis effluent of continuous PD patients. Then we assessed the role and mechanism of HDAC8 in peritoneal fibrosis progression in mouse model of peritoneal fibrosis induced by high glucose peritoneal dialysis fluid by using PCI-34051. In vitro, TGF-β1 or IL-4 were used to stimulate human peritoneal mesothelial cells (HPMCs) or RAW264.7 cells to establish two cell injury models to further explore the role and mechanism of HDAC8 in epithelial-mesenchymal transition (EMT) and macrophage polarization. RESULTS: We found that HDAC8 expressed highly in the peritoneum from patients with PD-related peritonitis. We further revealed that the level of HDAC8 in the dialysate increased over time, and HDAC8 was positively correlated with TGF-β1 and vascular endothelial growth factor (VEGF), and negatively correlated with cancer antigen 125. In mouse model of peritoneal fibrosis induced by high glucose dialysate, administration of PCI-34051 (a selective HDAC8 inhibitor) significantly prevented the progression of peritoneal fibrosis. Treatment with PCI-34051 blocked the phosphorylation of epidermal growth factor receptor (EGFR) and the activation of its downstream signaling pathways ERK1/2 and STAT3/HIF-1α. Inhibition of HDAC8 also reduced apoptosis. In vitro, HDAC8 silencing with PCI-34051 or siRNA inhibited TGF-β1-induced EMT and apoptosis in HPMCs. In addition, continuous high glucose dialysate or IL-4 stimulation induced M2 macrophage polarization. Blockade of HDAC8 reduced M2 macrophage polarization by inhibiting the activation of STAT6 and PI3K/Akt signaling pathways. CONCLUSIONS: We demonstrated that HDAC8 promoted the EMT of HPMCs via EGFR/ERK1/2/STAT3/HIF-1α, induced M2 macrophage polarization via STAT6 and PI3K/Akt signaling pathways, and ultimately accelerated the process of peritoneal fibrosis.

93. The association between genetic variants at 3'-UTR and 5'-URR of HLA-G gene and the clinical outcomes of patients with leukemia receiving hematopoietic stem cell transplantation.

Front Immunol

2023 Feb 23

Chen DP, Wang PN, Hour AL

94. Common framework mutations impact antibody interfacial dynamics and flexibility.

Front Immunol

2023 Feb 23

Rhodes ER, Faris JG, Petersen BM

95. An arginase1- and PD-L1-derived peptide-based vaccine for myeloproliferative neoplasms: A first-in-man clinical trial.

Front Immunol

2023 Feb 23

Grauslund JH, Holmström MO, Martinenaite E

INTRODUCTION: Arginase-1 (ARG1) and Programed death ligand-1 (PD-L1) play a vital role in immunosuppression in myeloproliferative neoplasms (MPNs) and directly inhibit T-cell activation and proliferation. We previously identified spontaneous T-cell responses towards PD-L1 and ARG1 derived peptide epitopes in patients with MPNs. In the present First-in-Man study we tested dual vaccinations of ARG1- derived and PD-L1-derived peptides, combined with Montanide ISA-51 as adjuvant, in patients with Janus Kinase 2 (JAK2) V617F-mutated MPN. METHODS: Safety and efficacy of vaccination with ARG1- derived and PD-L1-derived peptides with montanide as an adjuvant was tested in 9 patients with MPN The primary end point was safety and toxicity evaluation. The secondary end point was assessment of the immune response to the vaccination epitope (www.clinicaltrials.gov identifier NCT04051307). RESULTS: The study included 9 patients with JAK2-mutant MPN of which 8 received all 24 planned vaccines within a 9-month treatment period. Patients reported only grade 1 and 2 vaccine related adverse events. No alterations in peripheral blood counts were identified, and serial measurements of the JAK2V617F allelic burden showed that none of the patients achieved a molecular response during the treatment period. The vaccines induced strong immune responses against both ARG1 and PD-L1- derived epitopes in the peripheral blood of all patients, and vaccine-specific skin-infiltrating lymphocytes from 5/6 patients could be expanded in vitro after a delayed-type hypersensitivity test. In two patients we also detected both ARG1- and PD-L1-specific T cells in bone marrow samples at the end of trial. Intracellular cytokine staining revealed IFNγ and TNFγ producing CD4+- and CD8+- T cells specific against both vaccine epitopes. Throughout the study, the peripheral CD8/CD4 ratio increased significantly, and the CD8+ TEMRA subpopulation was enlarged. We also identified a significant decrease in PD-L1 mRNA expression in CD14+ myeloid cells in the peripheral blood in all treated patients and a decrease in ARG1 mRNA expression in bone marrow of 6 out of 7 evaluated patients. CONCLUSION: Overall, the ARG1- and PD-L1-derived vaccines were safe and tolerable and induced strong T-cell responses in all patients. These results warrant further studies of the vaccine in other settings or in combination with additional immune-activating treatments.

96. The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis.

Front Immunol

2023 Feb 23

Batal I, Khairallah P, Weins A

97. Advances in immune checkpoint inhibitors induced-cardiotoxicity.

Front Immunol

2023 Feb 23

Li X, Peng W, Wu J

98. Transcriptional reprogramming of natural killer cells by vaccinia virus shows both distinct and conserved features with mCMV.

Front Immunol

2023 Feb 23

Depierreux DM, Smith GL, Ferguson BJ.

99. Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes.

Front Immunol

2023 Feb 23

Yin W, Luo S, Qiu J

100. E3-ubiquitin ligases and recent progress in osteoimmunology.

Front Immunol

2023 Feb 23

Asano Y, Matsumoto Y, Wada J

101. Dose and route of administration determine the efficacy of prophylactic immunotherapy for peanut allergy in a Brown Norway rat model.

Front Immunol

2023 Feb 23

Sztuk TKS, Rigby NM, Nørskov-Nielsen L

INTRODUCTION: Allergen-specific immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy. Yet, prophylactic IT remains unexplored despite early introduction of peanut in infancy was shown to prevent allergy. There is a need to understand how allergens interact with the immune system depending on the route of administration, and how different dosages of allergen may protect from sensitisation and a clinical active allergy. Here we compared peanut allergen delivery via the oral, sublingual (SL), intragastric (IG) and subcutaneous (SC) routes for the prevention of peanut allergy in Brown Norway (BN) rats. METHODS: BN rats were administered PBS or three different doses of peanut protein extract (PPE) via either oral IT (OIT), SLIT, IGIT or SCIT followed by intraperitoneal (IP) injections of PPE to assess the protection from peanut sensitisation. The development of IgE and IgG1 responses to PPE and the major peanut allergens were evaluated by ELISAs. The clinical response to PPE was assessed by an ear swelling test (EST) and proliferation was assessed by stimulating splenocytes with PPE. RESULTS: Low and medium dose OIT (1 and 10 mg) and all doses of SCIT (1, 10, 100 µg) induced sensitisation to PPE, whereas high dose OIT (100 mg), SLIT (10, 100 or 1000 µg) or IGIT (1, 10 and 100 mg) did not. High dose OIT and SLIT as well as high and medium dose IGIT prevented sensitisation from the following IP injections of PPE and suppressed PPE-specific IgE levels in a dose-dependent manner. Hence, administration of peanut protein via different routes confers different risks for sensitisation and protection from peanut allergy development. Overall, the IgE levels toward the individual major peanut allergens followed the PPE-specific IgE levels. DISCUSSION: Collectively, this study showed that the preventive effect of allergen-specific IT is determined by the interplay between the specific site of PPE delivery for presentation to the immune system, and the allergen quantity, and that targeting and modulating tolerance mechanisms at specific mucosal sites may be a prophylactic strategy for prevention of peanut allergy.

102. Towards reproducible research in recurrent pregnancy loss immunology: Learning from cancer microenvironment deconvolution.

Front Immunol

2023 Feb 23

Betti M, Vizza E, Piccione E

103. Developing an m5C regulator-mediated RNA methylation modification signature to predict prognosis and immunotherapy efficacy in rectal cancer.

Front Immunol

2023 Feb 22

Zhang R, Gan W, Zong J

BACKGROUND: Currently, a very small number of patients with colorectal cancer (CRC) respond to immune checkpoint inhibitor (ICI) treatment. Therefore, there is an urgent need to investigate effective biomarkers to determine the responsiveness to ICI treatment. Recently, aberrant 5-methylcytosine (m5C) RNA modification has emerged as a key player in the pathogenesis of cancer. Thus, we aimed to explore the predictive signature based on m5C regulator-related genes for characterizing the immune landscapes and predicting the prognosis and response to therapies. METHODS: The Cancer Genome Atlas (TCGA) cohort was used as the training set, while GEO data sets, real-time quantitative PCR (RT-qPCR) analysis from paired frozen tissues, and immunohistochemistry (IHC) data from tissue microarray (TMA) were used for validation. We constructed a novel signature based on three m5C regulator-related genes in patients with rectal adenocarcinoma (READ) using a least absolute shrinkage and selection operator (LASSO)-Cox regression and unsupervised consensus clustering analyses. Additionally, we correlated the three-gene signature risk model with the tumor immune microenvironment, immunotherapy efficiency, and potential applicable drugs. RESULTS: The m5C methylation-based signature was an independent prognostic factor, where low-risk patients showed a stronger immunoreactivity phenotype and a superior response to ICI therapy. Conversely, the high-risk patients had enriched pathways of cancer hallmarks and presented immune-suppressive state, which demonstrated that they are more insensitive to immunotherapy. Additionally, the signature markedly correlated with drug susceptibility. CONCLUSIONS: We developed a reliable m5C regulator-based risk model to predict the prognosis, clarify the molecular and tumor microenvironment status, and identify patients who would benefit from immunotherapy or chemotherapy. Our study could provide vital guidance to improve prognostic stratification and optimize personalized therapeutic strategies for patients with rectal cancer.

104. Whole genome methylation combined with RNA-seq reveals the protective effects of Gualou-Xiebai herb pair in foam cells through DNA methylation mediated PI3K-AKT signaling pathway.

Front Immunol

2023 Feb 22

Jia Z, Mei J, Zhang Y

DNA methylation, including aberrant hypomethylation and hypermethylation, plays a significant role in atherosclerosis (AS); therefore, targeting the unbalanced methylation in AS is a potential treatment strategy. Gualou-xiebai herb pair (GXHP), a classic herb combination, have been used for the treatment of atherosclerotic-associated diseases in traditional Chinese medicine. However, the effects and underlying mechanism of GXHP on AS remain nebulous. In this study, the CCK-8 method was applied to determine the non-toxic treatment concentrations for GXHP. The formation of foam cells played a critical role in AS, so the foam cells model was established after RAW264.7 cells were treated with ox-LDL. The contents of total cholesterol (TC) and free cholesterol (FC) were determined by Gas chromatography-mass spectrometry (GC-MS). Enzyme-linked immunosorbent assay (ELISA) was used to check the expressions of inflammatory factors including IL-1β, TNF-α, and VCAM-1. Methyl-capture sequencing (MC-seq) and RNA-seq were applied to observe the changes in genome-wide DNA methylation and gene expression, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze differentially methylated genes (DMGs) and differentially expressed genes (DEGs). The targeted signaling pathway was selected and verified using western blotting (WB). The results showed that the lipids and inflammatory factors in foam cells significantly increased. GXHP significantly reduced the expression of TC, FC, and inflammatory factors. MC-seq and RNA-seq showed that GXHP not only corrected the aberrant DNA hypermethylation, but also DNA hypomethylation, thus restored the aberrant DEGs in foam cells induced by ox-LDL. GXHP treatment may target the PI3K-Akt signaling pathway. GXHP reduced the protein levels of phosphorylated(p)-PI3K and p-AKT in foam cells. Our data suggest that treatment with GXHP showed protective effects against AS through the inhibition of DNA methylation mediated PI3K-AKT signaling pathway, suggesting GXHP as a novel methylation-based agent.

105. ADCC: An underappreciated correlate of cross-protection against influenza?

Front Immunol

2023 Feb 22

de Vries RD, Hoschler K, Rimmelzwaan GF.

106. Prognostic value of the immunohistochemical score based on four markers in head and neck squamous cell carcinoma.

Front Immunol

2023 Feb 22

Xu QQ, Li QJ, Xu Z

107. Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning.

Front Immunol

2023 Feb 22

Xu M, Zhou H, Hu P

108. Specific cannabinoids revive adaptive immunity by reversing immune evasion mechanisms in metastatic tumours.

Front Immunol

2023 Feb 22

Dada S, Ellis SLS, Wood C

Emerging cancers are sculpted by neo-Darwinian selection for superior growth and survival but minimal immunogenicity; consequently, metastatic cancers often evolve common genetic and epigenetic signatures to elude immune surveillance. Immune subversion by metastatic tumours can be achieved through several mechanisms; one of the most frequently observed involves the loss of expression or mutation of genes composing the MHC-I antigen presentation machinery (APM) that yields tumours invisible to Cytotoxic T lymphocytes, the key component of the adaptive cellular immune response. Fascinating ethnographic and experimental findings indicate that cannabinoids inhibit the growth and progression of several categories of cancer; however, the mechanisms underlying these observations remain clouded in uncertainty. Here, we screened a library of cannabinoid compounds and found molecular selectivity amongst specific cannabinoids, where related molecules such as Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol can reverse the metastatic immune escape phenotype in vitro by inducing MHC-I cell surface expression in a wide variety of metastatic tumours that subsequently sensitizing tumours to T lymphocyte recognition. Remarkably, H3K27Ac ChIPseq analysis established that cannabigerol and gamma interferon induce overlapping epigenetic signatures and key gene pathways in metastatic tumours related to cellular senescence, as well as APM genes involved in revealing metastatic tumours to the adaptive immune response. Overall, the data suggest that specific cannabinoids may have utility in cancer immunotherapy regimens by overcoming immune escape and augmenting cancer immune surveillance in metastatic disease. Finally, the fundamental discovery of the ability of cannabinoids to alter epigenetic programs may help elucidate many of the pleiotropic medicinal effects of cannabinoids on human physiology.

109. Smoking is an independent but not a causal risk factor for moderate to severe psoriasis: A Mendelian randomization study of 105,912 individuals.

Front Immunol

2023 Feb 22

Näslund-Koch C, Vedel-Krogh S, Bojesen SE

110. Dietary factors and risk for asthma: A Mendelian randomization analysis.

Front Immunol

2023 Feb 22

Yang W, Yang Y, He L

111. Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming.

Front Immunol

2023 Feb 22

Bénard A, Hansen FJ, Uhle F

112. Emerging roles of the gut microbiota in cancer immunotherapy.

Front Immunol

2023 Feb 22

Shi Z, Li H, Song W

113. Pathological complete response to neoadjuvant tislelizumab plus chemotherapy in stage IIIB small cell lung cancer: A case report and literature review.

Front Immunol

2023 Feb 22

Zhou N, Chen Y, Huang Q

114. "Open Sesame" to the complexity of pattern recognition receptors of myeloid-derived suppressor cells in cancer.

Front Immunol

2023 Feb 22

Wang T, Hu Y, Dusi S

115. A tri-specific killer engager against mesothelin targets NK cells towards lung cancer.

Front Immunol

2023 Feb 22

Kennedy PR, Vallera DA, Ettestad B

116. HIV associated cell death: Peptide-induced apoptosis restricts viral transmission.

Front Immunol

2023 Feb 22

Chen Q, Zhao Y, Zhang Y

117. Phenotypic diversity of human adipose tissue-resident NK cells in obesity.

Front Immunol

2023 Feb 22

Haugstøyl ME, Cornillet M, Strand K

118. Interactions between PCSK9 and NLRP3 inflammasome signaling in atherosclerosis.

Front Immunol

2023 Feb 22

Wang Y, Fang D, Yang Q

119. The effects of microglia-associated neuroinflammation on Alzheimer's disease.

Front Immunol

2023 Feb 22

Wang C, Zong S, Cui X

120. Recent advances in the functional explorations of nuclear microRNAs.

Front Immunol

2023 Feb 22

Hu X, Yin G, Zhang Y

121. Head and neck dermatitis is exacerbated by Malassezia furfur colonization, skin barrier disruption, and immune dysregulation.

Front Immunol

2023 Feb 22

Chu H, Kim SM, Zhang K

INTRODUCTION & OBJECTIVES: Head and neck dermatitis (HND) is a refractory phenotype of atopic dermatitis (AD) and can be a therapeutic challenge due to lack of responsiveness to conventional treatments. Previous studies have suggested that the microbiome and fungiome may play a role in inducing HND, but the underlying pathogenic mechanisms remain unknown. This study aimed to determine the link between HND and fungiome and to examine the contribution of Malassezia furfur. MATERIALS AND METHODS: To identify the effect of the sensitization status of M. furfur on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of M. furfur, human keratinocytes and dermal endothelial cells were cultured with M. furfur and treated with Th2 cytokines. The downstream effects of various cytokines, including inflammation and angiogenesis, were investigated by real-time quantitative PCR. To identify the association between changes in lipid composition and M. furfur sensitization status, D-squame tape stripping was performed. Lipid composition was evaluated by focusing on ceramide species using liquid chromatography coupled with tandem mass spectrometry. RESULTS: Increased sensitization to M. furfur was observed in patients with HND. Additionally, sensitization to M. furfur was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with M. furfur produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/M. furfur co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-β, TNF-α, and IL-1β levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, M. furfur growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including Cutibacterium acnes, were not inhibited. CONCLUSIONS: Under decreased levels of ceramide in AD patients with HND, M. furfur would proliferate, which may enhance pro-inflammatory cytokine levels, angiogenesis, and tissue remodeling. Thus, it plays a central role in the pathogenesis of HND in AD.

122. Intervention strategies in early childhood to prevent celiac disease-a mini-review.

Front Immunol

2023 Feb 22

Andrén Aronsson C, Agardh D.

123. The use of bioinformatics methods to identify the effects of SARS-CoV-2 and influenza viruses on the regulation of gene expression in patients.

Front Immunol

2023 Feb 22

Sun Z, Ke L, Zhao Q

124. Mucosal immunization with Ad5-based vaccines protects Syrian hamsters from challenge with omicron and delta variants of SARS-CoV-2.

Front Immunol

2023 Feb 22

Braun MR, Martinez CI, Dora EG

SARS-CoV-2 variant clades continue to circumvent antibody responses elicited by vaccination or infection. Current parenteral vaccination strategies reduce illness and hospitalization, yet do not significantly protect against infection by the more recent variants. It is thought that mucosal vaccination strategies may better protect against infection by inducing immunity at the sites of infection, blocking viral transmission more effectively, and significantly inhibiting the evolution of new variants of concern (VOCs). In this study, we evaluated the immunogenicity and efficacy of a mucosally-delivered, non-replicating, adenovirus type 5-vectored vaccine that expresses the spike (S) gene of Wuhan (rAd5-S-Wuhan), delta (rAd5-S-delta), or omicron (rAd5-S-omicron) SARS-CoV-2 VOCs. Hamsters were immunized with these vaccines intranasally prior to challenge with omicron or delta variants. Additionally, one group was vaccinated by oral gavage with rAd5-S-Wuhan prior to challenge with the delta variant. Both intranasal and oral administration of rAd5-S-Wuhan generated cross-reactive serum IgG and mucosal IgA to all variant spike and RBD proteins tested. rAd5-S-omicron and rAd5-S-delta additionally elicited cross-reactive antibodies, though rAd5-S-omicron had significantly lower binding antibody levels except against its matched antigens. Two weeks after the final vaccination, hamsters were challenged with a SARS-CoV-2 variant; omicron or delta. Whether matched to the challenge or with rAd5-S-Wuhan, all vaccines protected hamsters from weight loss and lung pathology caused by challenge and significantly reduced viral shedding compared to placebo. Vaccination with rAd5-S-Wuhan provided significant protection, although there was an improved reduction in shedding and disease pathology in groups protected by the matched VOC vaccines. Nevertheless, Wuhan-based vaccination elicited the most cross-reactive antibody responses generally. Overall, heterologous vaccination via mucosal routes may be advantageous for second-generation vaccines.

125. Control of Mycobacterium avium subsp. paratuberculosis load within infected bovine monocyte-derived macrophages is associated with host genetics.

Front Immunol

2023 Feb 22

Badia-Bringué G, Canive M, Alonso-Hearn M.

The genetic loci influencing individual resistance to Mycobacterium avium subsp. paratuberculosis (MAP) infection are still largely unknown. In the current study, we searched for genetic loci associated with resistance to MAP infection by evaluating the performance of monocyte-derived macrophages (MDMs) isolated from the peripheral blood of 75 healthy Holsteins cows and infected ex vivo with MAP. Bacterial load (log colony-forming units, log CFUs) within MDMs was quantified at 2 h and 7 days p. i. using a BACTEC MGIT 960 instrument. In addition, the expression levels of some genes with important roles in the innate immune response including epiregulin (EREG), complement component C3 (C3), galectin-9 (Gal9), and nitric oxide (NO-) were measured in the supernatant of the infected cells. DNA from peripheral blood samples of the animals included in the study was isolated and genotyped with the EuroG MD bead Chip (44,779 single nucleotide-polymorphisms, SNPs). Linear mixed models were used to calculate the heritability (h2 ) estimates for each indicator of MDM performance, MAP load within MDMs and EREG, C3, Gal9, and NO-expression. After performing a genome-wide association study, the only phenotypes that showed SNPs with a significant association were the bacterial load within MDMs at 2 h (h2 = 0. 87) and 7 days (h2 = 0.83) p.i. A total of 6 SNPs, 5 candidate genes, and one microRNA on the Bos taurus chromosomes BTA2, BTA17, BTA18, and BTA21 were associated with MAP load at 2 h p.i. Overlap was seen in two SNPs associated with the log CFUs at 2 h and 7 d p.i. The identified SNPs had negative regression coefficients, and were, therefore, associated with a low bacterial load within MDMs. Some of the identified SNPs were located within QTLs previously associated with longevity, reproductive, and udder health traits. Some of the identified candidate genes; Oxysterol Binding Protein Like 6, Cysteine and Serine Rich Nuclear Protein 3, and the Coiled-Coil Domain Containing 92 regulate cellular cholesterol trafficking and efflux, apoptosis, and interferon production, respectively. Taken together, our results define a heritable and distinct immunogenetic profile in MAP-infected macrophages designed to limit bacterial load early after infection.

126. Association between serum folate levels and blood eosinophil counts in American adults with asthma: Results from NHANES 2011-2018.

Front Immunol

2023 Feb 22

Wen J, Wang C, Giri M

127. Enhancement of anti-tumor efficacy of immune checkpoint blockade by alpha-TEA.

Front Immunol

2023 Feb 22

Redmond WL, Kasiewicz MJ, Akporiaye ET.

128. Salivary IgA subtypes as novel disease biomarkers in systemic lupus erythematosus.

Front Immunol

2023 Feb 22

Romero-Ramírez S, Sosa-Hernández VA, Cervantes-Díaz R

129. Extracellular vesicles as potential biomarkers and treatment options for liver failure: A systematic review up to March 2022.

Front Immunol

2023 Feb 22

Lu W, Tang H, Li S

130. BATF sustains homeostasis and functionality of bone marrow Treg cells to preserve homeostatic regulation of hematopoiesis and development of B cells.

Front Immunol

2023 Feb 22

Tikka C, Beasley L, Xu C

131. The effects of conjugated linoleic acid supplementation on inflammatory cytokines and adipokines in adults: A GRADE-assessed systematic review and dose-response meta-analysis.

Front Immunol

2023 Feb 22

Rastgoo S, Shimi G, Shiraseb F

132. Interferon therapy and its association with depressive disorders - A review.

Front Immunol

2023 Feb 22

Lai JY, Ho JX, Kow ASF

133. Allogeneic hematopoietic stem cell transplantation in the COVID-19 era.

Front Immunol

2023 Feb 22

Bordat J, Maury S, Leclerc M.

134. Autoimmune pancreatitis: A bibliometric analysis from 2002 to 2022.

Front Immunol

2023 Feb 22

Zhang XD, Zhang Y, Zhao YZ

135. Evolution of antibody profiles against SARS-CoV-2 in experienced and naïve vaccinated elderly people.

Front Immunol

2023 Feb 22

Sanz-Muñoz I, López-Mongil R, Sánchez-Martínez J

136. Third COVID-19 vaccine dose for people with multiple sclerosis who did not seroconvert following two doses of BBIBP-CorV (Sinopharm) inactivated vaccine: A pilot study on safety and immunogenicity.

Front Immunol

2023 Feb 21

Sedaghat N, Etemadifar M, Lotfi N

137. Avidity engineering of human heavy-chain-only antibodies mitigates neutralization resistance of SARS-CoV-2 variants.

Front Immunol

2023 Feb 21

Du W, Janssens R, Mykytyn AZ

138. Self-assembled nanoparticles: A new platform for revolutionizing therapeutic cancer vaccines.

Front Immunol

2023 Feb 21

Shi T, Sun M, Lu C

139. ICAMs are dispensable for influenza clearance and anti-viral humoral and cellular immunity.

Front Immunol

2023 Feb 21

Kozlovski S, Regev O, Sapoznikov A

αLβ2 (LFA-1) mediated interactions with ICAM-1 and ICAM-2 predominate leukocyte-vascular interactions, but their functions in extravascular cell-cell communications is still debated. The roles of these two ligands in leukocyte trafficking, lymphocyte differentiation, and immunity to influenza infections were dissected in the present study. Surprisingly, double ICAM-1 and ICAM-2 knock out mice (herein ICAM-1/2-/- mice) infected with a lab adapted H1N1 influenza A virus fully recovered from infection, elicited potent humoral immunity, and generated normal long lasting anti-viral CD8+ T cell memory. Furthermore, lung capillary ICAMs were dispensable for both NK and neutrophil entry to virus infected lungs. Mediastinal lymph nodes (MedLNs) of ICAM-1/2-/- mice poorly recruited naïve T cells and B lymphocytes but elicited normal humoral immunity critical for viral clearance and effective CD8+ differentiation into IFN-γ producing T cells. Furthermore, whereas reduced numbers of virus specific effector CD8+ T cells accumulated inside infected ICAM-1/2-/- lungs, normal virus-specific TRM CD8+ cells were generated inside these lungs and fully protected ICAM-1/2-/- mice from secondary heterosubtypic infections. B lymphocyte entry to the MedLNs and differentiation into extrafollicular plasmablasts, producing high affinity anti-influenza IgG2a antibodies, were also ICAM-1 and ICAM-2 independent. A potent antiviral humoral response was associated with accumulation of hyper-stimulated cDC2s in ICAM null MedLNs and higher numbers of virus-specific T follicular helper (Tfh) cells generated following lung infection. Mice selectively depleted of cDC ICAM-1 expression supported, however, normal CTL and Tfh differentiation following influenza infection, ruling out essential co-stimulatory functions of DC ICAM-1 in CD8+ and CD4+ T cell differentiation. Collectively our findings suggest that lung ICAMs are dispensable for innate leukocyte trafficking to influenza infected lungs, for the generation of peri-epithelial TRM CD8+ cells, and long term anti-viral cellular immunity. In lung draining LNs, although ICAMs promote lymphocyte homing, these key integrin ligands are not required for influenza-specific humoral immunity or generation of IFN-γ effector CD8+ T cells. In conclusion, our findings suggest unexpected compensatory mechanisms that orchestrate protective anti-influenza immunity in the absence of vascular and extravascular ICAMs.

140. The potential regulatory role of the lncRNA-miRNA-mRNA axis in teleost fish.

Front Immunol

2023 Feb 21

Zhou Z, Leng C, Wang Z

141. Human monocyte-derived suppressive cells (HuMoSC) for cell therapy in giant cell arteritis.

Front Immunol

2023 Feb 21

Samson M, Genet C, Corbera-Bellalta M

142. Complementarity determining regions in SARS-CoV-2 hybrid immunity.

Front Immunol

2023 Feb 21

Frans G, Dillaerts D, Dehaemers T

143. Emerging role for interferons in respiratory viral infections and childhood asthma.

Front Immunol

2023 Feb 21

Bosco A.

144. C9 immunostaining as a tissue biomarker for periprosthetic joint infection diagnosis.

Front Immunol

2023 Feb 21

Meinshausen AK, Färber J, Illiger S

BACKGROUND: Culture-negative periprosthetic joint infections (PJI) are often false diagnosed as aseptic implant failure leading to unnecessary revision surgeries due to repeated infections. A marker to increase the security of e PJI diagnosis is therefore of great importance. The aim of this study was to test C9 immunostaining of periprosthetic tissue as a novel tissue-biomarker for a more reliable identification of PJI, as well as potential cross-reactivity. METHOD: We included 98 patients in this study undergoing septic or aseptic revision surgeries. Standard microbiological diagnosis was performed in all cases for classification of patients. Serum parameters including C-reactive protein (CRP) serum levels and white blood cell (WBC) count were included, and the periprosthetic tissue was immunostained for C9 presence. The amount of C9 tissue staining was evaluated in septic versus aseptic tissue and the amount of C9 staining was correlated with the different pathogens causing the infection. To exclude cross-reactions between C9 immunostaining and other inflammatory joint conditions, we included tissue samples of a separate cohort with rheumatoid arthritis, wear particles and chondrocalcinosis. RESULTS: The microbiological diagnosis detected PJI in 58 patients; the remaining 40 patients were classified as aseptic. Serum CRP values were significantly increased in the PJI cohort. Serum WBC was not different between septic and aseptic cases. We found a significant increase in C9 immunostaining in the PJI periprosthetic tissue. To test the predictive value of C9 as biomarker for PJI we performed a ROC analyses. According to the Youden's criteria C9 is a very good biomarker for PJI detection with a sensitivity of 89% and a specificity of 75% and an AUC of 0.84. We did not observe a correlation of C9 staining with the pathogen causing the PJI. However, we observed a cross reactivity with the inflammatory joint disease like rheumatoid arthritis and different metal wear types. In addition, we did not observe a cross reactivity with chondrocalcinosis. CONCLUSION: Our study identifies C9 as a potential tissue-biomarker for the identification of PJI using immunohistological staining of tissue biopsies. The use of C9 staining could help to reduce the number of false negative diagnoses of PJI.

145. Microbiology and immune mechanisms associated with male infertility.

Front Immunol

2023 Feb 21

Chen J, Chen J, Fang Y

146. Integration of bulk RNA sequencing and single-cell analysis reveals a global landscape of DNA damage response in the immune environment of Alzheimer's disease.

Front Immunol

2023 Feb 21

Lai Y, Lin H, Chen M

BACKGROUND: We developed a novel system for quantifying DNA damage response (DDR) to help diagnose and predict the risk of Alzheimer's disease (AD). METHODS: We thoroughly estimated the DDR patterns in AD patients Using 179 DDR regulators. Single-cell techniques were conducted to validate the DDR levels and intercellular communications in cognitively impaired patients. The consensus clustering algorithm was utilized to group 167 AD patients into diverse subgroups after a WGCNA approach was employed to discover DDR-related lncRNAs. The distinctions between the categories in terms of clinical characteristics, DDR levels, biological behaviors, and immunological characteristics were evaluated. For the purpose of choosing distinctive lncRNAs associated with DDR, four machine learning algorithms, including LASSO, SVM-RFE, RF, and XGBoost, were utilized. A risk model was established based on the characteristic lncRNAs. RESULTS: The progression of AD was highly correlated with DDR levels. Single-cell studies confirmed that DDR activity was lower in cognitively impaired patients and was mainly enriched in T cells and B cells. DDR-related lncRNAs were discovered based on gene expression, and two different heterogeneous subtypes (C1 and C2) were identified. DDR C1 belonged to the non-immune phenotype, while DDR C2 was regarded as the immune phenotype. Based on various machine learning techniques, four distinctive lncRNAs associated with DDR, including FBXO30-DT, TBX2-AS1, ADAMTS9-AS2, and MEG3 were discovered. The 4-lncRNA based riskScore demonstrated acceptable efficacy in the diagnosis of AD and offered significant clinical advantages to AD patients. The riskScore ultimately divided AD patients into low- and high-risk categories. In comparison to the low-risk group, high-risk patients showed lower DDR activity, accompanied by higher levels of immune infiltration and immunological score. The prospective medications for the treatment of AD patients with low and high risk also included arachidonyltrifluoromethane and TTNPB, respectively. CONCLUSIONS: In conclusion, immunological microenvironment and disease progression in AD patients were significantly predicted by DDR-associated genes and lncRNAs. A theoretical underpinning for the individualized treatment of AD patients was provided by the suggested genetic subtypes and risk model based on DDR.

147. Heterogeneity of antibody-secreting cells infiltrating autoimmune tissues.

Front Immunol

2023 Feb 21

Giovannini D, Belbezier A, Baillet A

148. Malaria and leishmaniasis: Updates on co-infection.

Front Immunol

2023 Feb 21

Ornellas-Garcia U, Cuervo P, Ribeiro-Gomes FL.

149. Generating enhanced mucosal immunity against Bordetella pertussis: current challenges and new directions.

Front Immunol

2023 Feb 21

Caulfield AD, Callender M, Harvill ET.

150. Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development.

Front Immunol

2023 Feb 21

Zhou Y, Qu J, Sun X

151. The effect of Abi3 locus deletion on the progression of Alzheimer's disease-related pathologies.

Front Immunol

2023 Feb 21

Karahan H, Smith DC, Kim B

152. Association between the systemic immune-inflammation index and kidney stone: A cross-sectional study of NHANES 2007-2018.

Front Immunol

2023 Feb 21

Di X, Liu S, Xiang L

153. Effects of systemic inflammation and frailty on survival in elderly cancer patients: Results from the INSCOC study.

Front Immunol

2023 Feb 20

Zhang Q, Wang Z, Song M

BACKGROUND: Frailty and systemic inflammation are parameters, which are easy to evaluate, can be used to predict disease outcomes, and are potentially modifiable. The combination of frailty and inflammation-based data may help identify elderly cancer patients predisposed to adverse clinical outcomes. The aim of this study was to examine the association of systemic inflammation and frailty at admission, and to determine whether these risk factors interact and may predict the survival of elderly cancer patients. METHODS: A prospective Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) with 5,106 elderly cancer patients admitted from 2013 through 2020 was included in this study. The primary marker of inflammation was the neutrophil-to-lymphocyte ratio (NLR), with the reference group having NLR<3, which indicated no inflammation. Frailty was assessed using the FRAIL scale, and patients with≥3 positives out of a total of five components were assumed to be frail. The primary outcome was all-cause mortality. We classified participants according to the presence (or absence) of frailty and high inflammation and assessed their association with overall survival using the Cox proportional hazards models adjusted for demographic, tumor, and treatment factors. RESULTS: Among the 5,106 patients enrolled in the study, 3396 individuals (66.51%) were male and the mean( ± SD) age at diagnosis was 70.92( ± 5.34). Over a median of 33.5 months follow-up, we observed 2,315 deaths. Increasing NLR was associated with frailty (compared with NLR<3, odds ratio=1.23, 95%CI=1.08-1.41 for NLR≥3). An NLR≥3 and frailty independently predicted the overall survival [hazard ratio(HR)=1.35, 95%CI=1.24-1.47 and HR=1.38, 95%CI=1.25-1.52, respectively). Patients with both frailty and NLR≥3 had the lowest overall survival(HR=1.83, 95%CI=1.59-2.04) than patients with no risk factors. The mortality rate increased with the presence of the frailty components. CONCLUSIONS: Systemic inflammation was positively associated with frailty. Frail elderly cancer patients with elevated systemic inflammation had low survival rate.

154. Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events.

Front Immunol

2023 Feb 20

Liu X, Tang H, Zhou Q

155. The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diffuse large B-cell lymphoma.

Front Immunol

2023 Feb 20

Lin Z, Mao D, Jin C

BACKGROUND: Gut microbiota characteristics in patients with diffuse large B-cell lymphoma (DLBCL) are reportedly different when compared with the healthy population and it remains unclear if the gut microbiota affects host immunity and clinical disease features. This research investigated the gut microbiota in patients with untreated DLBCL and analyzed its correlation with patient clinical characteristics, humoral, and cell immune status. METHODS: Thirty-five patients with untreated DLBCL and 20 healthy controls (HCs) were recruited to this study and microbiota differences in stool samples were analyzed by 16S rDNA sequencing. Absolute ratios of immune cell subset counts in peripheral blood were detected by flow cytometry and peripheral blood cytokine levels were detected by enzyme-linked immunosorbent assay. Relationships between changes in patient microbiomes and clinical characteristics, such as clinical stage, international prognostic index (IPI) risk stratification, cell origin, organ involved and treatment responses were investigated and correlations between differential microbiota and host immune indices were analyzed. RESULTS: The alpha-diversity index of intestinal microecology in DLBCL patients was not significantly different when compared with HCs (P>0.05), nonetheless beta-diversity was significantly decreased (P=0.001). p_Proteobacteria were dominant in DLBCL, while p_Bacteroidetes abundance was significantly decreased when compared with HCs (P<0.05). Gut microbiota characteristics were identified that were associated with clinical features, such as tumor load, risk stratification and cell origin, and correlation analyses were performed between differential flora abundance associated with these clinical features and host immune status. The p_Firmicutes was positively correlated with absolute lymphocyte values, g_Prevotella_2 and s_un_g_Prevotella_2 were negatively correlated with absolute lymphocyte values, T cell counts and CD4 cell counts, while g_Pyramidobacter, s_un_g_Pyramidobacter, and f_Peptostreptococcaceae were negatively correlated with IgA. CONCLUSIONS: Dominant gut microbiota, abundance, diversity, and structure in DLBCL were influenced by the disease, correlated with patient immune status and this suggested that the microecology-immune axis may be involved in regulating lymphoma development. In the future, it may be possible to improve immune function in patients with DLBCL by regulating the gut microbiota, improve treatment response rates and increase patient survival rates.

156. Pre-immunotherapy radiotherapy enhanced the efficacy of multi-line sintilimab in unresectable advanced esophageal squamous cell carcinoma.

Front Immunol

2023 Feb 20

Xu S, Xu X, Zhu H.

BACKGROUND: The use of immunotherapy for the treatment of esophageal squamous cell carcinoma (ESCC) is gradually increasing. In this retrospective study, we evaluated the efficacy and explored potential factors of prognosis in multi-line sintilimab for unresectable advanced ESCC. METHODS: All pathological specimens were available from our Department of Pathology. We performed PD-L1 immunohistochemical staining of surgical or puncture specimens from 133 patients. We evaluated the efficacy of multi-line sintilimab and found potential factors according to multivariate analysis. We assessed the relationship between radiotherapy and immunotherapy, and according to whether patients had received radiotherapy within 3 months prior to immunotherapy, we attempted to analyze differences in progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 133 patients were enrolled in this retrospective study between January 2019 and December 2021. The median follow-up was 16.1 months. All patients were treated with at least two cycles of sintilimab. Of all patients, a total of 74 experienced disease progression, with a median progression-free survival of 9.0 months (95% CI 7.701-10.299). We found that pre-immunotherapy radiotherapy was a possible predictor that affected the prognosis of multi-line sintilimab and that 3 months was a significant cutoff. A total of 128 patients (96.2%) had received radiotherapy prior to immunotherapy. Of those patients, 89 (66.9%) had received radiation therapy within 3 months prior to immunotherapy. PFS was considerably longer in patients who were treated within 3 months of radiotherapy than in patients who did not receive radiation therapy within 3 months of radiation therapy prior to immunotherapy (median progression-free survival 10.0 months [95% CI 8.030-11.970] vs. 5.0 months [95% CI 2.755-7.245]). Among all patients, the median overall survival was 14.9 months (95% CI 12.558-17.242). Overall survival was significantly longer in patients who had previously received radiotherapy within 3 months prior to immunotherapy than in those who had not (median overall survival 15.3 months [95% CI 13.724-16.876] vs. 12.2 months [10.001-14.399]. CONCLUSION: Based on this retrospective study, sintilimab is a significant option for patients with unresectable advanced ESCC who have been previously treated, and pre-immunotherapy radiotherapy within 3 months enhanced the efficacy.

157. Evaluating SARS-CoV-2 antibody reactivity to natural exposure and inactivated vaccination with peptide microarrays.

Front Immunol

2023 Feb 20

Zheng P, Ma J, Yang J

158. Cutaneous manifestations associated with immune checkpoint inhibitors.

Front Immunol

2023 Feb 20

Watanabe T, Yamaguchi Y.

159. A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component.

Front Immunol

2023 Feb 20

Yoshioka Y, Kobiyama K, Hayashi T

BACKGROUND: Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known. METHODS AND RESULTS: To characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component. CONCLUSIONS: This study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants.

160. CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies.

Front Immunol

2023 Feb 20

Zhang X, Zhang H, Lan H

161. The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome.

Front Immunol

2023 Feb 20

Wang Y, Zhu CL, Li P

Sepsis is defined as a life-threatening dysfunction due to a dysregulated host response to infection. It is a common and complex syndrome and is the leading cause of death in intensive care units. The lungs are most vulnerable to the challenge of sepsis, and the incidence of respiratory dysfunction has been reported to be up to 70%, in which neutrophils play a major role. Neutrophils are the first line of defense against infection, and they are regarded as the most responsive cells in sepsis. Normally, neutrophils recognize chemokines including the bacterial product N-formyl-methionyl-leucyl-phenylalanine (fMLP), complement 5a (C5a), and lipid molecules Leukotriene B4 (LTB4) and C-X-C motif chemokine ligand 8 (CXCL8), and enter the site of infection through mobilization, rolling, adhesion, migration, and chemotaxis. However, numerous studies have confirmed that despite the high levels of chemokines in septic patients and mice at the site of infection, the neutrophils cannot migrate to the proper target location, but instead they accumulate in the lungs, releasing histones, DNA, and proteases that mediate tissue damage and induce acute respiratory distress syndrome (ARDS). This is closely related to impaired neutrophil migration in sepsis, but the mechanism involved is still unclear. Many studies have shown that chemokine receptor dysregulation is an important cause of impaired neutrophil migration, and the vast majority of these chemokine receptors belong to the G protein-coupled receptors (GPCRs). In this review, we summarize the signaling pathways by which neutrophil GPCR regulates chemotaxis and the mechanisms by which abnormal GPCR function in sepsis leads to impaired neutrophil chemotaxis, which can further cause ARDS. Several potential targets for intervention are proposed to improve neutrophil chemotaxis, and we hope that this review may provide insights for clinical practitioners.

162. Therapeutic effects of mesenchymal stem cells and their derivatives in common skin inflammatory diseases: Atopic dermatitis and psoriasis.

Front Immunol

2023 Feb 20

Yang J, Xiao M, Ma K

163. Identification of a DRB3*011:01-restricted CD4(+) T cell response against bovine respiratory syncytial virus fusion protein.

Front Immunol

2023 Feb 20

Kaplan BS, Hofstetter AR, McGill JL

164. VISTA expression and patient selection for immune-based anticancer therapy.

Front Immunol

2023 Feb 20

Martin AS, Molloy M, Ugolkov A

165. Evaluation of multiple immune cells and patient outcomes in esophageal squamous cell carcinoma.

Front Immunol

2023 Feb 20

Wang H, Su C, Li Z

166. Interleukin-27-dependent transcriptome signatures during neonatal sepsis.

Front Immunol

2023 Feb 20

Povroznik JM, Akhter H, Vance JK

167. Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis.

Front Immunol

2023 Feb 20

Zhou Y, Li X, Ng L

OBJECTIVE: An analysis of the relationship between rheumatoid arthritis (RA) and copper death-related genes (CRG) was explored based on the GEO dataset. METHODS: Based on the differential gene expression profiles in the GSE93272 dataset, their relationship to CRG and immune signature were analysed. Using 232 RA samples, molecular clusters with CRG were delineated and analysed for expression and immune infiltration. Genes specific to the CRGcluster were identified by the WGCNA algorithm. Four machine learning models were then built and validated after selecting the optimal model to obtain the significant predicted genes, and validated by constructing RA rat models. RESULTS: The location of the 13 CRGs on the chromosome was determined and, except for GCSH. LIPT1, FDX1, DLD, DBT, LIAS and ATP7A were expressed at significantly higher levels in RA samples than in non-RA, and DLST was significantly lower. RA samples were significantly expressed in immune cells such as B cells memory and differentially expressed genes such as LIPT1 were also strongly associated with the presence of immune infiltration. Two copper death-related molecular clusters were identified in RA samples. A higher level of immune infiltration and expression of CRGcluster C2 was found in the RA population. There were 314 crossover genes between the 2 molecular clusters, which were further divided into two molecular clusters. A significant difference in immune infiltration and expression levels was found between the two. Based on the five genes obtained from the RF model (AUC = 0.843), the Nomogram model, calibration curve and DCA also demonstrated their accuracy in predicting RA subtypes. The expression levels of the five genes were significantly higher in RA samples than in non-RA, and the ROC curves demonstrated their better predictive effect. Identification of predictive genes by RA animal model experiments was also confirmed. CONCLUSION: This study provides some insight into the correlation between rheumatoid arthritis and copper mortality, as well as a predictive model that is expected to support the development of targeted treatment options in the future.

168. Autoantibodies against complement factor B in rheumatoid arthritis.

Front Immunol

2023 Feb 20

Matola AT, Fülöp A, Rojkovich B

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Many patients carry anti-citrullinated protein autoantibodies (ACPA). Overactivation of the complement system seems to be part of the pathogenesis of RA, and autoantibodies against the pathway initiators C1q and MBL, and the regulator of the complement alternative pathway, factor H (FH), were previously reported. Our aim was to analyze the presence and role of autoantibodies against complement proteins in a Hungarian RA cohort. To this end, serum samples of 97 ACPA-positive RA patients and 117 healthy controls were analyzed for autoantibodies against FH, factor B (FB), C3b, C3-convertase (C3bBbP), C1q, MBL and factor I. In this cohort, we did not detect any patient with FH autoantibodies but detected C1q autoantibodies in four patients, MBL autoantibodies in two patients and FB autoantibodies in five patients. Since the latter autoantibodies were previously reported in patients with kidney diseases but not in RA, we set out to further characterize such FB autoantibodies. The isotypes of the analyzed autoantibodies were IgG2, IgG3, IgGκ, IgGλ and their binding site was localized in the Bb part of FB. We detected in vivo formed FB-autoanti-FB complexes by Western blot. The effect of the autoantibodies on the formation, activity and FH-mediated decay of the C3 convertase in solid phase convertase assays was determined. In order to investigate the effect of the autoantibodies on complement functions, hemolysis assays and fluid phase complement activation assays were performed. The autoantibodies partially inhibited the complement-mediated hemolysis of rabbit red blood cells, inhibited the activity of the solid phase C3-convertase and C3 and C5b-9 deposition on complement activating surfaces. In summary, in ACPA-positive RA patients we identified FB autoantibodies. The characterized FB autoantibodies did not enhance complement activation, rather, they had inhibitory effect on complement. These results support the involvement of the complement system in the pathomechanism of RA and raise the possibility that protective autoantibodies may be generated in some patients against the alternative pathway C3 convertase. However, further analyses are needed to assess the exact role of such autoantibodies.

169. MicroRNA-183/96/182 cluster in immunity and autoimmunity.

Front Immunol

2023 Feb 20

Wang Z, Dai R, Ahmed SA.

170. SARS-COV-2 viroporins activate the NLRP3-inflammasome by the mitochondrial permeability transition pore.

Front Immunol

2023 Feb 20

Guarnieri JW, Angelin A, Murdock DG

BACKGROUND: Compared to healthy controls, severe COVID19 patients display increased levels of activated NLRP3-inflammasome (NLRP3-I) and interleukin (IL)-1β. SARS-CoV-2 encodes viroporin proteins E and Orf3a(2-E+2-3a) with homologs to SARS-CoV-1, 1-E+1-3a, which elevate NLRP3-I activation; by an unknown mechanism. Thus, we investigated how 2-E+2-3a activates the NLRP3-I to better understand the pathophysiology of severe COVID-19. METHODS: We generated a polycistronic expression-vector co-expressing 2-E+2-3a from a single transcript. To elucidate how 2-E+2-3a activates the NLRP3-I, we reconstituted the NLRP3-I in 293T cells and used THP1-derived macrophages to monitor the secretion of mature IL-1β. Mitochondrial physiology was assessed using fluorescent microscopy and plate reader assays, and the release of mitochondrial DNA (mtDNA) was detected from cytosolic-enriched fractions using Real-Time PCR. RESULTS: Expression of 2-E+2-3a in 293T cells increased cytosolic Ca++ and elevated mitochondrial Ca++, taken up through the MCUi11-sensitive mitochondrial calcium uniporter. Increased mitochondrial Ca++ stimulated NADH, mitochondrial reactive oxygen species (mROS) production and the release of mtDNA into the cytosol. Expression of 2-E+2-3a in NLRP3-I reconstituted 293T cells and THP1-derived macrophages displayed increased secretion of IL-1β. Increasing mitochondrial antioxidant defenses via treatment with MnTBAP or genetic expression of mCAT abolished 2-E+2-3a elevation of mROS, cytosolic mtDNA levels, and secretion of NLRP3-activated-IL-1β. The 2-E+2-3a-induced release of mtDNA and the secretion of NLRP3-activated-IL-1β were absent in cells lacking mtDNA and blocked in cells treated with the mitochondrial-permeability-pore(mtPTP)-specific inhibitor NIM811. CONCLUSION: Our findings revealed that mROS activates the release of mitochondrial DNA via the NIM811-sensitive mitochondrial-permeability-pore(mtPTP), activating the inflammasome. Hence, interventions targeting mROS and the mtPTP may mitigate the severity of COVID-19 cytokine storms.

171. Effects of Helicobacter pylori adhesin HopQ binding to CEACAM receptors in the human stomach.

Front Immunol

2023 Feb 20

Nguyen QA, Schmitt L, Mejías-Luque R

172. Identification of a novel senescence-associated signature to predict biochemical recurrence and immune microenvironment for prostate cancer.

Front Immunol

2023 Feb 20

Han C, Deng Y, Yang B

BACKGROUND: Prostate cancer (PCa) is an age-associated malignancy with high morbidity and mortality rate, posing a severe threat to public health. Cellular senescence, a specialized cell cycle arrest form, results in the secretion of various inflammatory mediators. In recent studies, senescence has shown an essential role in tumorigenesis and tumor development, yet the extensive effects of senescence in PCa have not been systematically investigated. Here, we aimed to develop a feasible senescence-associated prognosis model for early identification and appropriate management in patients with PCa. METHOD: The RNA sequence results and clinical information available from The Cancer Genome Atlas (TCGA) and a list of experimentally validated senescence-related genes (SRGs) from the CellAge database were first obtained. Then, a senescence-risk signature related with prognosis was constructed using univariate Cox and LASSO regression analysis. We calculated the risk score of each patient and divided them into high-risk and low-risk groups in terms of the median value. Furthermore, two datasets (GSE70770 and GSE46602) were used to assess the effects of the risk model. A nomogram was built by integrating the risk score and clinical characteristics, which was further verified using ROC curves and calibrations. Finally, we compared the differences in the tumor microenvironment (TME) landscape, drug susceptibility, and the functional enrichment among the different risk groups. RESULTS: We established a unique prognostic signature in PCa patients based on eight SRGs, including CENPA, ADCK5, FOXM1, TFAP4, MAPK, LGALS3, BAG3, and NOX4, and validated well prognosis-predictive power in independent datasets. The risk model was associated with age and TNM staging, and the calibration chart presented a high consistency in nomogram prediction. Additionally, the prognostic signature could serve as an independent prediction factor due to its high accuracy. Notably, we found that the risk score was positively associated with tumor mutation burden (TMB) and immune checkpoint, whereas negatively correlated with tumor immune dysfunction and exclusion (TIDE), suggesting that these patients with risk scores were more sensitive to immunotherapy. Drug susceptibility analysis revealed differences in the responses to general drugs (docetaxel, cyclophosphamide, 5-Fluorouracil, cisplatin, paclitaxel, and vincristine) were yielded between the two risk groups. CONCLUSION: Identifying the SRG-score signature may become a promising method for predicting the prognosis of patients with PCa and tailoring appropriate treatment strategies.

173. T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications.

Front Immunol

2023 Feb 20

Chi X, Luo S, Ye P

174. Comparative study on antibacterial characteristics of the multiple liver expressed antimicrobial peptides (LEAPs) in teleost fish.

Front Immunol

2023 Feb 20

Liu X, Hu YZ, Pan YR

175. Crosstalk between microbiome, regulatory T cells and HCA2 orchestrates the inflammatory response in a murine psoriasis model.

Front Immunol

2023 Feb 20

Schwarz A, Philippsen R, Piticchio SG

176. The melanoma tumor glyco-code impacts human dendritic cells' functionality and dictates clinical outcomes.

Front Immunol

2023 Feb 20

Sosa Cuevas E, Roubinet B, Mouret S

177. Unusual Talaromyces marneffei and Pneumocystis jirovecii coinfection in a child with a STAT1 mutation: A case report and literature review.

Front Immunol

2023 Feb 20

Yang Q, Yu C, Wu Y

178. Identification and characterization of immunoglobulin tau (IgT) in Asian Seabass (Lates calcarifer) and mucosal immune response to nervous necrosis virus.

Front Immunol

2023 Feb 20

Chan J, Carmen LCP, Lee SQ

179. A novel oral formulation of the melanocortin-1 receptor agonist PL8177 resolves inflammation in preclinical studies of inflammatory bowel disease and is gut restricted in rats, dogs, and humans.

Front Immunol

2023 Feb 20

Dodd J, Jordan R, Makhlina M

INTRODUCTION: PL8177 is a potent and selective agonist of the melanocortin 1 receptor (MC1R). PL8177 has shown efficacy in reversing intestinal inflammation in a cannulated rat ulcerative colitis model. To facilitate oral delivery, a novel, polymer-encapsulated formulation of PL8177 was developed. This formulation was tested in 2 rat ulcerative colitis models and evaluated for distribution, in vivo, in rats, dogs, and humans. METHODS: The rat models of colitis were induced by treatment with 2,4-dinitrobenzenesulfonic acid or dextran sulfate sodium. Single nuclei RNA sequencing of colon tissues was performed to characterize the mechanism of action. The distribution and concentration of PL8177 and the main metabolite within the GI tract after a single oral dose of PL8177 was investigated in rats and dogs. A phase 0 clinical study using a single microdose (70 µg) of [14C]-labeled PL8177 investigated the release of PL8177 in the colon of healthy men after oral administration. RESULTS: Rats treated with 50 µg oral PL8177 demonstrated significantly lower macroscopic colon damage scores and improvement in colon weight, stool consistency, and fecal occult blood vs the vehicle without active drug. Histopathology analysis resulted in the maintenance of intact colon structure and barrier, reduced immune cell infiltration, and increased enterocytes with PL8177 treatment. Transcriptome data show that oral PL8177 50 µg treatment causes relative cell populations and key gene expressions levels to move closer to healthy controls. Compared with vehicle, treated colon samples show negative enrichment of immune marker genes and diverse immune-related pathways. In rats and dogs, orally administered PL8177 was detected at higher amounts in the colon vs upper GI tract. [14C]-PL8177 and the main metabolite were detected in the feces but not in the plasma and urine in humans. This suggests that the parent drug [14C]-PL8177 was released from the polymer formulation and metabolized within the GI tract, where it would be expected to exert its effect. CONCLUSION: Collectively, these findings support further research into the oral formulation of PL8177 as a possible therapeutic for GI inflammatory diseases in humans.

180. scRNA-seq reveals aging-related immune cell types and regulators in vaginal wall from elderly women with pelvic organ prolapse.

Front Immunol

2023 Feb 20

Miao Y, Wen J, Wang L

181. Prediction of early treatment response to the combination therapy of TACE plus lenvatinib and anti-PD-1 antibody immunotherapy for unresectable hepatocellular carcinoma: Multicenter retrospective study.

Front Immunol

2023 Feb 17

Li S, Wu J, Wu J

182. The efficacy and safety of neoadjuvant immunotherapy in resectable locally advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis.

Front Immunol

2023 Feb 17

He W, Wang C, Li C

OBJECTIVE: This systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). BACKGROUND: Several studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking. METHODS: Studies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0. RESULTS: Thirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26-0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31-0.65; nICT: 0.29, 95% CI: 0.26-0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1-2 and 3-4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56-0.84) and 0.16 (95% CI: 0.09-0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3-4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17-0.77; nICT: 0.14, 95% CI: 0.07-0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15-0.53; cisplatin: 0.04, 95% CI: 0.01-0.09; p<0.01). CONCLUSION: Neoadjuvant immunotherapy has good efficacy and safety profiles in patients with locally advanced ESCC. Additional RCTs with long-term survival data are warranted.

183. Therapeutic equine hyperimmune antibodies with high and broad-spectrum neutralizing activity protect rodents against SARS-CoV-2 infection.

Front Immunol

2023 Feb 17

Li E, Han Q, Bi J

184. Neoadjuvant immune checkpoint inhibition in the management of glioblastoma: Exploring a new frontier.

Front Immunol

2023 Feb 17

Frederico SC, Darling C, Bielanin JP

Brain tumors are one of the leading causes of cancer related death in both the adult and pediatric patient population. Gliomas represent a cohort of brain tumors derived from glial cell lineages which include astrocytomas, oligodendrogliomas and glioblastomas (GBMs). These tumors are known to grow aggressively and have a high lethality with GBM being the most aggressive tumor in this group. Currently, few treatment options exist for GBM outside of surgical resection, radiation therapy and chemotherapy. While these measures have been shown to marginally improve patient survival, patients, especially those diagnosed with GBM, often experience a recurrence of their disease. Following disease recurrence, treatment options become more limited as additional surgical resections can pose life threatening risk to the patient, patients may be ineligible for additional radiation, and the recurrent tumor may be resistant to chemotherapy. Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy as many patients with cancers residing outside the central nervous system (CNS) have experienced a survival benefit from this treatment modality. It has often been observed that this survival benefit is increased following neoadjuvant administration of immune checkpoint inhibitors as tumor antigen is still present in the patient which enables a more robust anti-tumor immune response. Interestingly, results for ICI-based studies for patients with GBM have been largely disappointing which is a stark contrast from the success this treatment modality has had in non-central nervous system cancers. In this review, we will discuss the various benefits of neoadjuvant immune checkpoint inhibition such as how this approach reduces tumor burden and allows for a greater induction of an anti-tumor immune response. Additionally, we will discuss several non-CNS cancers where neoadjuvant immune checkpoint inhibition has been successful and discuss why we believe this approach may provide a survival benefit for GBM patients. We hope this manuscript will foster future studies aimed at exploring whether this approach may be beneficial for patients diagnosed with GBM.

185. Aerobic and facultative anaerobic Klebsiella pneumoniae strains establish mutual competition and jointly promote Musca domestica development.

Front Immunol

2023 Feb 17

Zhang K, Wang S, Yao D

186. Biosynthesized selenium nanoparticles to rescue coccidiosis-mediated oxidative stress, apoptosis and inflammation in the jejunum of mice.

Front Immunol

2023 Feb 17

Abdel-Gaber R, Hawsah MA, Al-Otaibi T

One of the most crucial approaches for treating human diseases, particularly parasite infections, is nanomedicine. One of the most significant protozoan diseases that impact farm and domestic animals is coccidiosis. While, amprolium is one of the traditional anticoccidial medication, the advent of drug-resistant strains of Eimeria necessitates the development of novel treatments. The goal of the current investigation was to determine whether biosynthesized selenium nanoparticles (Bio-SeNPs) using Azadirachta indica leaves extract might treat mice with Eimeria papillata infection in the jejunal tissue. Five groups of seven mice each were used, as follows: Group 1: Non-infected-non-treated (negative control). Group 2: Non-infected treated group with Bio-SeNPs (0.5 mg/kg of body weight). Groups 3-5 were orally inoculated with 1×103 sporulated oocysts of E. papillata. Group 3: Infected-non-treated (positive control). Group 4: Infected and treated group with Bio-SeNPs (0.5 mg/kg). Group 5: Infected and treated group with the Amprolium. Groups 4 and 5 daily received oral administration (for 5 days) of Bio-SeNPs and anticoccidial medication, respectively, after infection. Bio-SeNPs caused a considerable reduction in oocyst output in mice feces (97.21%). This was also accompanied by a significant reduction in the number of developmental parasitic stages in the jejunal tissues. Glutathione reduced (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels were dramatically reduced by the Eimeria parasite, whereas, nitric oxide (NO) and malonaldehyde (MDA) levels were markedly elevated. The amount of goblet cells and MUC2 gene expression were used as apoptotic indicators, and both were considerably downregulated by infection. However, infection markedly increased the expression of inflammatory cytokines (IL-6 and TNF-α) and the apoptotic genes (Caspase-3 and BCL2). Bio-SeNPs were administrated to mice to drastically lower body weight, oxidative stress, and inflammatory and apoptotic indicators in the jejunal tissue. Our research thus showed the involvement of Bio-SeNPs in protecting mice with E. papillata infections against jejunal damage.

187. Adipose tissue aging is regulated by an altered immune system.

Front Immunol

2023 Feb 17

Zhang YX, Ou MY, Yang ZH

188. Sequencing technology as a major impetus in the advancement of studies into rheumatism: A bibliometric study.

Front Immunol

2023 Feb 17

Huang R, Tang J, Wang S

BACKGROUND: Rheumatism covers a wide range of diseases with complex clinical manifestations and places a tremendous burden on humans. For many years, our understanding of rheumatism was seriously hindered by technology constraints. However, the increasing application and rapid advancement of sequencing technology in the past decades have enabled us to study rheumatism with greater accuracy and in more depth. Sequencing technology has made huge contributions to the field and is now an indispensable component and powerful tool in the study of rheumatism. METHODS: Articles on sequencing and rheumatism, published from 1 January 2000 to 25 April 2022, were retrieved from the Web of Science™ (Clarivate™, Philadelphia, PA, USA) database. Bibliometrix, the open-source tool, was used for the analysis of publication years, countries, authors, sources, citations, keywords, and co-words. RESULTS: The 1,374 articles retrieved came from 62 countries and 350 institutions, with a general increase in article numbers during the last 22 years. The leading countries in terms of publication numbers and active cooperation with other countries were the USA and China. The most prolific authors and most popular documents were identified to establish the historiography of the field. Popular and emerging research topics were assessed by keywords and co-occurrence analysis. Immunological and pathological process in rheumatism, classification, risks and susceptibility, and biomarkers for diagnosis were among the hottest themes for research. CONCLUSIONS: Sequencing technology has been widely applied in the study of rheumatism and propells research in the area of discovering novel biomarkers, related gene patterns and physiopathology. We suggest that further efforts be made to advance the study of genetic patterns related to rheumatic susceptibility, pathogenesis, classification and disease activity, and novel biomarkers.

189. Case report: Discovery of a de novo FAM111B pathogenic variant in a patient with an APECED-like clinical phenotype.

Front Immunol

2023 Feb 17

Ferré EMN, Yu Y, Oikonomou V

190. The role of peroxisome proliferator-activated receptors in the modulation of hyperinflammation induced by SARS-CoV-2 infection: A perspective for COVID-19 therapy.

Front Immunol

2023 Feb 17

Hasankhani A, Bahrami A, Tavakoli-Far B

191. The protein kinase R modifies gut physiology to limit colitis.

Front Immunol

2023 Feb 17

Yim HCH, Chakrabarti A, Kessler S

192. An integrated co-expression network analysis reveals novel genetic biomarkers for immune cell infiltration in chronic kidney disease.

Front Immunol

2023 Feb 17

Xia J, Hou Y, Cai A

BACKGROUND: Chronic kidney disease (CKD) is characterized by persistent damage to kidney function or structure. Progression to end-stage leads to adverse effects on multiple systems. However, owing to its complex etiology and long-term cause, the molecular basis of CKD is not completely known. METHODS: To dissect the potential important molecules during the progression, based on CKD databases from Gene Expression Omnibus, we used weighted gene co-expression network analysis (WGCNA) to identify the key genes in kidney tissues and peripheral blood mononuclear cells (PBMC). Correlation analysis of these genes with clinical relevance was evaluated based on Nephroseq. Combined with a validation cohort and receiver operating characteristic curve (ROC), we found the candidate biomarkers. The immune cell infiltration of these biomarkers was evaluated. The expression of these biomarkers was further detected in folic acid-induced nephropathy (FAN) murine model and immunohistochemical staining. RESULTS: In total, eight genes (CDCP1, CORO1C, DACH1, GSTA4, MAFB, TCF21, TGFBR3, and TGIF1) in kidney tissue and six genes (DDX17, KLF11, MAN1C1, POLR2K, ST14, and TRIM66) in PBMC were screened from co-expression network. Correlation analysis of these genes with serum creatinine levels and estimated glomerular filtration rate from Nephroseq showed a well clinical relevance. Validation cohort and ROC identified TCF21, DACH1 in kidney tissue and DDX17 in PBMC as biomarkers for the progression of CKD. Immune cell infiltration analysis revealed that DACH1 and TCF21 were correlated with eosinophil, activated CD8 T cell, activated CD4 T cell, while the DDX17 was correlated with neutrophil, type-2 T helper cell, type-1 T helper cell, mast cell, etc. FAN murine model and immunohistochemical staining confirmed that these three molecules can be used as genetic biomarkers to distinguish CKD patients from healthy people. Moreover, the increase of TCF21 in kidney tubules might play important role in the CKD progression. DISCUSSION: We identified three promising genetic biomarkers which could play important roles in the progression of CKD.

193. Altered lipid metabolites accelerate early dysfunction of T cells in HIV-infected rapid progressors by impairing mitochondrial function.

Front Immunol

2023 Feb 17

Li SY, Yin LB, Ding HB

194. Multi-omics analysis reveals genomic, clinical and immunological features of SARS-CoV-2 virus target genes in pan-cancer.

Front Immunol

2023 Feb 17

Liao Y, Wang J, Zou J

195. Thermoneutral housing shapes hepatic inflammation and damage in mouse models of non-alcoholic fatty liver disease.

Front Immunol

2023 Feb 17

Oates JR, Sawada K, Giles DA

196. Extracorporeal photopheresis as an immunomodulatory treatment modality for chronic GvHD and the importance of emerging biomarkers.

Front Immunol

2023 Feb 17

Bojanic I, Worel N, Pacini CP

197. Analysis of the conserved protective epitopes of hemagglutinin on influenza A viruses.

Front Immunol

2023 Feb 17

Jiao C, Wang B, Chen P

198. Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study.

Front Immunol

2023 Feb 17

Amin NS, Abd El-Aziz MK, Hamed M

BACKGROUND: Multiple sclerosis (MS) is characterized by a complex etiology that is reflected in the lack of consistently predictable treatment responses across patients of seemingly similar characteristics. Approaches to demystify the underlying predictors of aberrant treatment responses have made use of genome-wide association studies (GWAS), with imminent progress made in identifying single nucleotide polymorphisms (SNPs) associated with MS risk, disease progression, and treatment response. Ultimately, such pharmacogenomic studies aim to utilize the approach of personalized medicine to maximize patient benefit and minimize rate of disease progression. OBJECTIVE: Very limited research is available around the long intergenic non-coding RNA (linc)00513, recently being reported as a novel positive regulator of the type-1 interferon (IFN) pathway, following its overexpression in the presence of two polymorphisms: rs205764 and rs547311 in the promoter region of this gene. We attempt to provide data on the prevalence of genetic variations at rs205764 and rs547311 in Egyptian MS patients, and correlate these polymorphisms with the patients' responses to disease-modifying treatments. METHODS: Genomic DNA from 144 RRMS patients was isolated and analyzed for genotypes at the positions of interest on linc00513 using RT-qPCR. Genotype groups were compared with regards to their response to treatment; additional secondary clinical parameters including the estimated disability status score (EDSS), and onset of the disease were examined in relation to these polymorphisms. RESULTS: Polymorphisms at rs205764 were associated with a significantly higher response to fingolimod and a significantly lower response to dimethylfumarate. Moreover, the average EDSS of patients carrying polymorphisms at rs547311 was significantly higher, whereas no correlation appeared to exist with the onset of MS. CONCLUSION: Understanding the complex interplay of factors influencing treatment response is pivotal in MS. One of the factors contributing to a patient's response to treatment, as well as disease disability, may be polymorphisms on non-coding genetic material, such as rs205764 and rs547311 on linc00513. Through this work, we propose that genetic polymorphisms may partially drive disease disability and inconsistent responses to treatment in MS; we also aim to draw attention towards genetic approaches, such as screening for specific polymorphisms, to possibly direct treatment choices in such a complex disease.

199. Precision immunointerception of EGFR-driven tumorigenesis for lung cancer prevention.

Front Immunol

2023 Feb 17

Pan J, Xiong D, Zhang Q

200. PHLDA1 modulates microglial response and NLRP3 inflammasome signaling following experimental subarachnoid hemorrhage.

Front Immunol

2023 Feb 17

Lai J, Chen G, Wu Z

201. Emerging role of interaction between m6A and main ncRNAs in gastrointestinal (GI) cancers.

Front Immunol

2023 Feb 17

Xu Y, Yu X, Guo W

202. Prospects and feasibility of synergistic therapy with radiotherapy, immunotherapy, and DNA methyltransferase inhibitors in non-small cell lung cancer.

Front Immunol

2023 Feb 17

Jie C, Li R, Cheng Y

203. Inulin prebiotic reinforces host cancer immunosurveillance via ɣδ T cell activation.

Front Immunol

2023 Feb 17

Boucher E, Plazy C, Richard ML

204. Lymphoid stromal cells - potential implications for the pathogenesis of CVID.

Front Immunol

2023 Feb 17

Cousin VN, Perez GF, Payne KJ

205. Targeting matrix metalloproteases in diabetic wound healing.

Front Immunol

2023 Feb 17

Chen J, Qin S, Liu S

206. Capturing the multifaceted function of adipose tissue macrophages.

Front Immunol

2023 Feb 16

Matz AJ, Qu L, Karlinsey K

207. Case report: Immunological characteristics of de novo ulcerative colitis in a child post COVID-19.

Front Immunol

2023 Feb 16

Morita A, Imagawa K, Tagawa M

208. The roles of COX-2 in protozoan infection.

Front Immunol

2023 Feb 16

Wang X, Chen J, Zheng J.

209. Immunoglobulin M-degrading enzyme of Streptococcus suis (Ide (Ssuis) ) impairs porcine B cell signaling.

Front Immunol

2023 Feb 16

Breitfelder AK, Schrödl W, Rungelrath V

210. Immunological priming of mesenchymal stromal/stem cells and their extracellular vesicles augments their therapeutic benefits in experimental graft-versus-host disease via engagement of PD-1 ligands.

Front Immunol

2023 Feb 16

Hackel A, Vollmer S, Bruderek K

211. Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies.

Front Immunol

2023 Feb 16

Besbassi H, Garcia-Fogeda I, Quinlivan M

212. T-cells engineered with a novel VHH-based chimeric antigen receptor against CD19 exhibit comparable tumoricidal efficacy to their FMC63-based counterparts.

Front Immunol

2023 Feb 16

Nasiri F, Safarzadeh Kozani P, Rahbarizadeh F.

213. Lipidome modulation by dietary omega-3 polyunsaturated fatty acid supplementation or selective soluble epoxide hydrolase inhibition suppresses rough LPS-accelerated glomerulonephritis in lupus-prone mice.

Front Immunol

2023 Feb 16

Favor OK, Chauhan PS, Pourmand E

INTRODUCTION: Lipopolysaccharide (LPS)-accelerated autoimmune glomerulonephritis (GN) in NZBWF1 mice is a preclinical model potentially applicable for investigating lipidome-modulating interventions against lupus. LPS can be expressed as one of two chemotypes: smooth LPS (S-LPS) or rough LPS (R-LPS) which is devoid of O-antigen polysaccharide sidechain. Since these chemotypes differentially affect toll-like receptor 4 (TLR4)-mediated immune cell responses, these differences may influence GN induction. METHODS: We initially compared the effects of subchronic intraperitoneal (i.p.) injection for 5 wk with 1) Salmonella S-LPS, 2) Salmonella R-LPS, or 3) saline vehicle (VEH) (Study 1) in female NZBWF1 mice. Based on the efficacy of R-LPS in inducing GN, we next used it to compare the impact of two lipidome-modulating interventions, ω-3 polyunsaturated fatty acid (PUFA) supplementation and soluble epoxide hydrolase (sEH) inhibition, on GN (Study 2). Specifically, effects of consuming ω-3 docosahexaenoic acid (DHA) (10 g/kg diet) and/or the sEH inhibitor 1-(4-trifluoro-methoxy-phenyl)-3-(1-propionylpiperidin-4-yl) urea (TPPU) (22.5 mg/kg diet ≈ 3 mg/kg/day) on R-LPS triggering were compared. RESULTS: In Study 1, R-LPS induced robust elevations in blood urea nitrogen, proteinuria, and hematuria that were not evident in VEH- or S-LPS-treated mice. R-LPS-treated mice further exhibited kidney histopathology including robust hypertrophy, hyperplasia, thickened membranes, lymphocytic accumulation containing B and T cells, and glomerular IgG deposition consistent with GN that was not evident in VEH- or SLPS-treated groups. R-LPS but not S-LPS induced spleen enlargement with lymphoid hyperplasia and inflammatory cell recruitment in the liver. In Study 2, resultant blood fatty acid profiles and epoxy fatty acid concentrations reflected the anticipated DHA- and TPPU-mediated lipidome changes, respectively. The relative rank order of R-LPS-induced GN severity among groups fed experimental diets based on proteinuria, hematuria, histopathologic scoring, and glomerular IgG deposition was: VEH/CON< R-LPS/DHA ≈ R-LPS/TPPU<<< R-LPS/TPPU+DHA ≈ R-LPS/CON. In contrast, these interventions had modest-to- negligible effects on R-LPS-induced splenomegaly, plasma antibody responses, liver inflammation, and inflammation-associated kidney gene expression. DISCUSSION: We show for the first time that absence of O-antigenic polysaccharide in R-LPS is critical to accelerated GN in lupus-prone mice. Furthermore, intervention by lipidome modulation through DHA feeding or sEH inhibition suppressed R-LPS-induced GN; however, these ameliorative effects were greatly diminished upon combining the treatments.

214. Primate liver tissue substrate in indirect immunofluorescence diagnostics for patients with dermatitis herpetiformis and celiac disease.

Front Immunol

2023 Feb 16

Schauer F, Tasiopoulou G, Schuster D

215. Role of the granzyme family in rheumatoid arthritis: Current Insights and future perspectives.

Front Immunol

2023 Feb 16

Zheng Y, Zhao J, Shan Y

216. Performance of an interferon-γ release assay-based test for cell-mediated immunity to SARS-CoV-2.

Front Immunol

2023 Feb 16

Fonseca Brito L, Tödter S, Kottlau J

217. Brief report: Assessment of mucosal barrier integrity using serological biomarkers in preclinical stages of rheumatoid arthritis.

Front Immunol

2023 Feb 16

Gilbert BTP, Lamacchia C, Amend L

218. Regulatory T cell enhancement in adults with cystic fibrosis receiving Elexacaftor/Tezacaftor/Ivacaftor therapy.

Front Immunol

2023 Feb 16

Westhölter D, Raspe J, Uebner H

219. Emerging mechanisms and functions of inflammasome complexes in teleost fish.

Front Immunol

2023 Feb 16

Chang MX.

220. Development and validation of a radiomics-based nomogram for predicting a major pathological response to neoadjuvant immunochemotherapy for patients with potentially resectable non-small cell lung cancer.

Front Immunol

2023 Feb 16

Liu C, Zhao W, Xie J

221. Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment.

Front Immunol

2023 Feb 16

Zhang N, Yao H, Zhang Z

222. Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy.

Front Immunol

2023 Feb 16

Zhang L, Chen Z, Wang L

223. Beclin-1 dependent autophagy improves renal outcomes following Unilateral Ureteral Obstruction (UUO) injury.

Front Immunol

2023 Feb 16

Lopez-Soler RI, Nikouee A, Kim M

BACKGROUND: Interstitial Fibrosis and Tubular Atrophy (IFTA) is the most common cause of long-term graft failure following renal transplant. One of the hallmarks of IFTA is the development of interstitial fibrosis and loss of normal renal architecture. In this study, we evaluated the role of autophagy initiation factor Beclin-1 in protecting against post-renal injury fibrosis. METHODS: Adult male wild type (WT) C57BL/6 mice were subjected to Unilateral Ureteral Obstruction (UUO), and kidney tissue samples were harvested at 72-hour, 1- and 3-week post-injury. The UUO-injured and uninjured kidney samples were examined histologically for fibrosis, autophagy flux, inflammation as well activation of the Integrated Stress Response (ISR). We compared WT mice with mice carrying a forced expression of constitutively active mutant form of Beclin-1, Becn1F121A/F121A . RESULTS: In all experiments, UUO injury induces a progressive development of fibrosis and inflammation. These pathological signs were diminished in Becn1F121A/F121A mice. In WT animals, UUO caused a strong blockage of autophagy flux, indicated by continuously increases in LC3II accompanied by an over 3-fold accumulation of p62 1-week post injury. However, increases in LC3II and unaffected p62 level by UUO were observed in Becn1F121A/F121A mice, suggesting an alleviation of disrupted autophagy. Beclin-1 F121A mutation causes a significant decrease in phosphorylation of inflammatory STING signal and limited production of IL6 and IFNγ, but had little effect on TNF-α, in response to UUO. Furthermore, activation of ISR signal cascade was detected in UUO-injured in kidneys, namely the phosphorylation signals of elF2S1 and PERK in addition to the stimulated expression of ISR effector ATF4. However, Becn1F121A/F121A mice did not reveal signs of elF2S1 and PERK activation under the same condition and had a dramatically reduced ATF level at 3-week post injury. CONCLUSIONS: The results suggest that UUO causes a insufficient, maladaptive renal autophagy, which triggered downstream activation of inflammatory STING pathway, production of cytokines, and pathological activation of ISR, eventually leading to the development of fibrosis. Enhancing autophagy via Beclin-1 improved renal outcomes with diminished fibrosis, via underlying mechanisms of differential regulation of inflammatory mediators and control of maladaptive ISR.

224. The intestine: A highly dynamic microenvironment for IgA plasma cells.

Front Immunol

2023 Feb 16

Pracht K, Wittner J, Kagerer F

225. Immunotherapy for hepatocellular carcinoma recurrence after liver transplantation, can we harness the power of immune checkpoint inhibitors?

Front Immunol

2023 Feb 16

Jiang J, Huang H, Chen R

226. IL-32 is induced by activation of toll-like receptors in multiple myeloma cells.

Front Immunol

2023 Feb 16

Aass KR, Tryggestad SS, Mjelle R

227. Dynamics of cell cycle proteins involved in Toxoplasma gondii-induced bovine NET formation.

Front Immunol

2023 Feb 16

Velásquez ZD, Peixoto R, Gärtner U

228. Donor derived hematopoietic stem cell niche transplantation facilitates mixed chimerism mediated donor specific tolerance.

Front Immunol

2023 Feb 16

Zhang W, Wang Y, Zhong F

229. Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma.

Front Immunol

2023 Feb 16

Chintala NK, Choe JK, McGee E

BACKGROUND: The attenuated, genetically engineered vaccinia virus has been shown to be a promising oncolytic virus for the treatment of patients with solid tumors, through both direct cytotoxic and immune-activating effects. Whereas systemically administered oncolytic viruses can be neutralized by pre-existing antibodies, locoregionally administered viruses can infect tumor cells and generate immune responses. We conducted a phase I clinical trial to investigate the safety, feasibility and immune activating effects of intrapleural administration of oncolytic vaccinia virus (NCT01766739). METHODS: Eighteen patients with malignant pleural effusion due to either malignant pleural mesothelioma or metastatic disease (non-small cell lung cancer or breast cancer) underwent intrapleural administration of the oncolytic vaccinia virus using a dose-escalating method, following drainage of malignant pleural effusion. The primary objective of this trial was to determine a recommended dose of attenuated vaccinia virus. The secondary objectives were to assess feasibility, safety and tolerability; evaluate viral presence in the tumor and serum as well as viral shedding in pleural fluid, sputum, and urine; and evaluate anti-vaccinia virus immune response. Correlative analyses were performed on body fluids, peripheral blood, and tumor specimens obtained from pre- and post-treatment timepoints. RESULTS: Treatment with attenuated vaccinia virus at the dose of 1.00E+07 plaque-forming units (PFU) to 6.00E+09 PFU was feasible and safe, with no treatment-associated mortalities or dose-limiting toxicities. Vaccinia virus was detectable in tumor cells 2-5 days post-treatment, and treatment was associated with a decrease in tumor cell density and an increase in immune cell density as assessed by a pathologist blinded to the clinical observations. An increase in both effector (CD8+, NK, cytotoxic cells) and suppressor (Tregs) immune cell populations was observed following treatment. Dendritic cell and neutrophil populations were also increased, and immune effector and immune checkpoint proteins (granzyme B, perforin, PD-1, PD-L1, and PD-L2) and cytokines (IFN-γ, TNF-α, TGFβ1 and RANTES) were upregulated. CONCLUSION: The intrapleural administration of oncolytic vaccinia viral therapy is safe and feasible and generates regional immune response without overt systemic symptoms. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01766739, identifier NCT01766739.

230. The epidemic of the multiresistant dermatophyte Trichophyton indotineae has reached China.

Front Immunol

2023 Feb 16

Jia S, Long X, Hu W

231. LIS1, a glyco-humanized swine polyclonal anti-lymphocyte globulin, as a novel induction treatment in solid organ transplantation.

Front Immunol

2023 Feb 16

Rousse J, Royer PJ, Evanno G

232. Case report: HLA-haploidentical HSCT rescued with donor lymphocytes infusions in a patient with X-linked chronic granulomatous disease.

Front Immunol

2023 Feb 16

Scheiermann J, Künkele A, von Stackelberg A

233. Translatome analyses by bio-orthogonal non-canonical amino acid labeling reveal that MR1-activated MAIT cells induce an M1 phenotype and antiviral programming in antigen-presenting monocytes.

Front Immunol

2023 Feb 16

Jakob J, Kröger A, Klawonn F

MAIT cells are multifunctional innate-like effector cells recognizing bacterial-derived vitamin B metabolites presented by the non-polymorphic MHC class I related protein 1 (MR1). However, our understanding of MR1-mediated responses of MAIT cells upon their interaction with other immune cells is still incomplete. Here, we performed the first translatome study of primary human MAIT cells interacting with THP-1 monocytes in a bicellular system. We analyzed the interaction between MAIT and THP-1 cells in the presence of the activating 5-OP-RU or the inhibitory Ac-6-FP MR1-ligand. Using bio-orthogonal non-canonical amino acid tagging (BONCAT) we were able to enrich selectively those proteins that were newly translated during MR1-dependent cellular interaction. Subsequently, newly translated proteins were measured cell-type-specifically by ultrasensitive proteomics to decipher the coinciding immune responses in both cell types. This strategy identified over 2,000 MAIT and 3,000 THP-1 active protein translations following MR1 ligand stimulations. Translation in both cell types was found to be increased by 5-OP-RU, which correlated with their conjugation frequency and CD3 polarization at MAIT cell immunological synapses in the presence of 5-OP-RU. In contrast, Ac-6-FP only regulated a few protein translations, including GSK3B, indicating an anergic phenotype. In addition to known effector responses, 5-OP-RU-induced protein translations uncovered type I and type II Interferon-driven protein expression profiles in both MAIT and THP-1 cells. Interestingly, the translatome of THP-1 cells suggested that activated MAIT cells can impact M1/M2 polarization in these cells. Indeed, gene and surface expression of CXCL10, IL-1β, CD80, and CD206 confirmed an M1-like phenotype of macrophages being induced in the presence of 5-OP-RU-activated MAIT cells. Furthermore, we validated that the Interferon-driven translatome was accompanied by the induction of an antiviral phenotype in THP-1 cells, which were found able to suppress viral replication following conjugation with MR1-activated MAIT cells. In conclusion, BONCAT translatomics extended our knowledge of MAIT cell immune responses at the protein level and discovered that MR1-activated MAIT cells are sufficient to induce M1 polarization and an anti-viral program of macrophages.

234. Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity.

Front Immunol

2023 Feb 16

Lu H, Cao W, Zhang L

One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 105 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants' HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.

235. The prognostic effect of sixteen malnutrition/inflammation-based indicators on the overall survival of chemotherapy patients.

Front Immunol

2023 Feb 16

Liu T, Liu C, Deng L

236. Targeting the recurrent Rac1P29S neoepitope in melanoma with heterologous high-affinity T cell receptors.

Front Immunol

2023 Feb 16

Immisch L, Papafotiou G, Gallarín Delgado N

237. Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?

Front Immunol

2023 Feb 16

Lechuga S, Braga-Neto MB, Naydenov NG

238. Targeting tumor-associated macrophages with STING agonism improves the antitumor efficacy of osimertinib in a mouse model of EGFR-mutant lung cancer.

Front Immunol

2023 Feb 16

Lin Z, Wang Q, Jiang T

239. Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases.

Front Immunol

2023 Feb 16

Santos FM, Ciordia S, Mesquita J

INTRODUCTION: Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD. METHODS: To unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4). RESULTS AND DISCUSSION: Post-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. Pathway analysis indicates that mediators of complement, coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and monitored by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins could differentiate between these vitreoretinal diseases. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (complement C2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).

240. A tool for evaluating heterogeneity in avidity of polyclonal antibodies.

Front Immunol

2023 Feb 16

Li K, Dodds M, Spreng RL

241. Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study.

Front Immunol

2023 Feb 16

Wang K, Xiang YJ, Yu HM

242. A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade.

Front Immunol

2023 Feb 16

Novick D.

243. Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients.

Front Immunol

2023 Feb 16

Bulnes-Ramos Á, Pozo-Balado MM, Olivas-Martínez I

244. Lung T cell response in COVID-19.

Front Immunol

2023 Feb 16

Shakiba MH, Gemünd I, Beyer M

245. Case report: Electrocardiographic changes in pembrolizumab-induced fatal myocarditis.

Front Immunol

2023 Feb 16

Nishiyama K, Morikawa K, Shinozaki Y

246. Knowledge mapping of image-guided tumor ablation and immunity: A bibliometric analysis.

Front Immunol

2023 Feb 15

Shen H, Wang L, Zhang Y

BACKGROUND: Various ablation techniques have been successfully applied in tumor therapy by locally destroying tumor. In the process of tumor ablation, a large number of tumor cell debris is released, which can be used as a source of tumor antigens and trigger a series of immune responses. With the deepening of the research on the immune microenvironment and immunotherapy, researches exploring tumor ablation and immunity are continuously published. However, no research has systematically analyzed the intellectual landscape and emerging trends for tumor ablation and immunity using scientometric analysis. Therefore, this study aimed to conduct a bibliometric analysis to quantify and identify the status quo and trend of tumor ablation and immunity. METHODS: Data of publications were downloaded from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to conduct bibliometric analysis to evaluate the contribution and co-occurrence relationship of different countries/regions, institutions and authors in the field, and to determine the research hotspots in this field. RESULTS: By searching in the database, a total of 3531 English articles published between 2012 and 2021 were obtained. We observed rapid growth in the number of publications since 2012. The two most active countries were China and the United States, with more than 1,000 articles. Chinese Academy of Sciences contributed the most publications (n = 153). Jibing Chen and Xianzheng Zhang might have a keen interest in tumor ablation and immunity, with more publications (n = 14; n = 13). Among the top 10 co-cited authors, Castano AP (284 citations) was ranked first, followed by Agostinis P (270 citations) and Chen Qian (246 citations). According to the co-occurrence and cluster analysis, the results indicated that the focus of research was "photothermal therapy" and "immune checkpoint blockade". CONCLUSIONS: In the past decade, the neighborhood of tumor ablation domain immunity has been paid more and more attention. Nowadays, the research hotspots in this field are mainly focused on exploring the immunological mechanism in photothermal therapy to improve its efficacy, and the combination of ablation therapy and immune checkpoint inhibitor therapy.

Front Immunol

2023 Feb 15

Li M, Long X, Bu W

248. Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers.

Front Immunol

2023 Feb 15

Zheng X, Gu H, Cao X

BACKGROUND: Tislelizumab is an anti-programmed cell death 1 (PD-1) monoclonal antibody engineered to minimize binding to Fcγ receptors. It has been used to treat several solid tumors. However, its efficacy and toxicity, and the predictive and prognostic value of baseline hematological parameters in patients with recurrent or metastatic cervical cancer (R/M CC) receiving tislelizumab remain unclear. METHODS: We reviewed 115 patients treated for R/M CC with tislelizumab from March 2020 to June 2022 in our institute. The antitumor activity of tislelizumab was assessed using RECIST v1.1. Associations between the baseline hematological parameters and efficacy of tislelizumab in these patients were analyzed. RESULTS: With a median follow-up of 11.3 months (range, 2.2-28.7), the overall response rate was 39.1% (95% CI, 30.1-48.2) and the disease control rate was 77.4% (95% CI, 69.6-85.2). The median progression-free survival (PFS) was 19.6 months (95% CI, 10.7 to not reached). The median overall survival (OS) was not reached. Treatment-related adverse events (TRAEs) of any grade occurred in 81.7% of the patients and only 7.0% of the patients experienced grade 3 or 4 TRAEs. Univariate and multivariate regression analyses showed that the level of pretreatment serum C-reactive protein (CRP) was an independent risk factor for the response (complete or partial response) to tislelizumab and the PFS of R/M CC patients treated with tislelizumab (P = 0.0001 and P = 0.002, respectively). R/M CC patients with elevated baseline CRP levels had a short PFS (P = 0.0005). Additionally, the CRP-to-albumin ratio (CAR) was an independent risk factor for the PFS and OS of R/M CC patients treated with tislelizumab (P = 0.001 and P = 0.031, respectively). R/M CC patients with an elevated baseline CAR had short PFS and OS (P < 0.0001 and P = 0.0323, respectively). CONCLUSIONS: Tislelizumab showed promising antitumor activity and tolerable toxicity in patients with R/M CC. The baseline serum CRP levels and CAR showed potential for predicting the efficacy of tislelizumab and the prognosis of R/M CC patients receiving tislelizumab.

249. Repeatability of metabolic tumor burden and lesion glycolysis between clinical readers.

Front Immunol

2023 Feb 15

Choi JW, Dean EA, Lu H

250. CD83 expressed by macrophages is an important immune checkpoint molecule for the resolution of inflammation.

Front Immunol

2023 Feb 15

Peckert-Maier K, Langguth P, Strack A

251. Occlusion preconditioned mice are resilient to hypobaric hypoxia-induced myocarditis and arrhythmias due to enhanced immunomodulation, metabolic homeostasis, and antioxidants defense.

Front Immunol

2023 Feb 15

Adzika GK, Mprah R, Rizvi R

BACKGROUND: Sea-level residents experience altitude sickness when they hike or visit altitudes above ~2,500 m due to the hypobaric hypoxia (HH) conditions at such places. HH has been shown to drive cardiac inflammation in both ventricles by inducing maladaptive metabolic reprogramming of macrophages, which evokes aggravated proinflammatory responses, promoting myocarditis, fibrotic remodeling, arrhythmias, heart failure, and sudden deaths. The use of salidroside or altitude preconditioning (AP) before visiting high altitudes has been extensively shown to exert cardioprotective effects. Even so, both therapeutic interventions have geographical limitations and/or are inaccessible/unavailable to the majority of the population as drawbacks. Meanwhile, occlusion preconditioning (OP) has been extensively demonstrated to prevent hypoxia-induced cardiomyocyte damage by triggering endogenous cardioprotective cascades to mitigate myocardial damage. Herein, with the notion that OP can be conveniently applied anywhere, we sought to explore it as an alternative therapeutic intervention for preventing HH-induced myocarditis, remodeling, and arrhythmias. METHODS: OP intervention (6 cycles of 5 min occlusion with 200 mmHg for 5 min and 5 min reperfusion at 0 mmHg - applying to alternate hindlimb daily for 7 consecutive days) was performed, and its impact on cardiac electric activity, immunoregulation, myocardial remodeling, metabolic homeostasis, oxidative stress responses, and behavioral outcomes were assessed before and after exposure to HH in mice. In humans, before and after the application of OP intervention (6 cycles of 5 min occlusion with 130% of systolic pressure and 5 min reperfusion at 0 mmHg - applying to alternate upper limb daily for 6 consecutive days), all subjects were assessed by cardiopulmonary exercise testing (CPET). RESULTS: Comparing the outcomes of OP to AP intervention, we observed that similar to the latter, OP preserved cardiac electric activity, mitigated maladaptive myocardial remodeling, induced adaptive immunomodulation and metabolic homeostasis in the heart, enhanced antioxidant defenses, and conferred resistance against HH-induce anxiety-related behavior. Additionally, OP enhanced respiratory and oxygen-carrying capacity, metabolic homeostasis, and endurance in humans. CONCLUSIONS: Overall, these findings demonstrate that OP is a potent alternative therapeutic intervention for preventing hypoxia-induced myocarditis, cardiac remodeling, arrhythmias, and cardiometabolic disorders and could potentially ameliorate the progression of other inflammatory, metabolic, and oxidative stress-related diseases.

252. Guillain-Barre syndrome following COVID-19 vaccines: A review of literature.

Front Immunol

2023 Feb 15

Yu M, Nie S, Qiao Y

OBJECTIVE: This study aimed to retrospectively analyze reported Guillain-Barré syndrome (GBS) cases that occurred after COVID-19 vaccination. METHODS: Case reports of GBS following COVID-19 vaccination that were published before May 14, 2022, were retrieved from PubMed. The cases were retrospectively analyzed for their basic characteristics, vaccine types, the number of vaccination doses before onset, clinical manifestations, laboratory test results, neurophysiological examination results, treatment, and prognosis. RESULTS: Retrospective analysis of 60 case reports revealed that post-COVID-19 vaccination GBS occurred mostly after the first dose of the vaccination (54 cases, 90%) and was common for DNA vaccination (38 cases, 63%), common in middle-aged and elderly people (mean age: 54.5 years), and also common in men (36 cases, 60%). The mean time from vaccination to onset was 12.3 days. The classical GBS (31 cases, 52%) was the major clinical classification and the AIDP subtype (37 cases, 71%) was the major neurophysiological subtype, but the positive rate of anti-ganglioside antibodies was low (7 cases, 20%). Bilateral facial nerve palsy (76% vs 18%) and facial palsy with distal paresthesia (38% vs 5%) were more common for DNA vaccination than for RNA vaccination. CONCLUSION: After reviewing the literature, we proposed a possible association between the risk of GBS and the first dose of the COVID-19 vaccines, especially DNA vaccines. The higher rate of facial involvement and a lower positive rate of anti-ganglioside antibodies may be a characteristic feature of GBS following COVID-19 vaccination. The causal relationship between GBS and COVID-19 vaccination remains speculative, more research is needed to establish an association between GBS and COVID-19 vaccination. We recommend surveillance for GBS following vaccination, because it is important in determining the true incidence of GBS following COVID-19 vaccination, as well as in the development of a more safer vaccine.

253. The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment.

Front Immunol

2023 Feb 15

Keerthana CK, Rayginia TP, Shifana SC

Adenosine monophosphate-activated protein kinase (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. AMPK contributes to diverse metabolic and physiological effects besides its fundamental role in glucose and lipid metabolism. Aberrancy in AMPK signaling is one of the determining factors which lead to the development of chronic diseases such as obesity, inflammation, diabetes, and cancer. The activation of AMPK and its downstream signaling cascades orchestrate dynamic changes in the tumor cellular bioenergetics. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways. In addition, AMPK plays a central role in potentiating the phenotypic and functional reprogramming of various classes of immune cells which reside in the tumor microenvironment (TME). Furthermore, AMPK-mediated inflammatory responses facilitate the recruitment of certain types of immune cells to the TME, which impedes the development, progression, and metastasis of cancer. Thus, AMPK appears to play an important role in the regulation of anti-tumor immune response by regulating the metabolic plasticity of various immune cells. AMPK effectuates the metabolic modulation of anti-tumor immunity via nutrient regulation in the TME and by virtue of its molecular crosstalk with major immune checkpoints. Several studies including that from our lab emphasize on the role of AMPK in regulating the anticancer effects of several phytochemicals, which are potential anticancer drug candidates. The scope of this review encompasses the significance of the AMPK signaling in cancer metabolism and its influence on the key drivers of immune responses within the TME, with a special emphasis on the potential use of phytochemicals to target AMPK and combat cancer by modulating the tumor metabolism.

254. Chicken CH25H inhibits ALV-J replication by promoting cellular autophagy.

Front Immunol

2023 Feb 15

Xie T, Feng M, Zhang X

255. Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus.

Front Immunol

2023 Feb 15

Wen L, Zhang B, Wu X

256. Case report: Unusual development of hepatocellular carcinoma during immunosuppressive treatments against rheumatoid arthritis overlapping Sjögren's syndrome; cirrhotic steatohepatitis with liver inflammation and fibrosis lurks in autoimmune disorders.

Front Immunol

2023 Feb 15

Yoshida S, Fujita M, Ishigame T

257. Red blood cells in proliferative kidney disease-rainbow trout (Oncorhynchus mykiss) infected by Tetracapsuloides bryosalmonae harbor IgM(+) red blood cells.

Front Immunol

2023 Feb 15

Chan JTH, Picard-Sánchez A, Majstorović J

258. Subtyping based on immune cell fractions reveal heterogeneity of cardiac fibrosis in end-stage heart failure.

Front Immunol

2023 Feb 15

Zou S, Khoo BL.

259. Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study.

Front Immunol

2023 Feb 15

Xu XJ, Lang JD, Yang J

BACKGROUND: Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD. METHODS: A cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from ex vivo stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features. RESULTS: The autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of Selenomonadales, Negatiyicutes, Veillonellaceae and Verrucomicrobiaceae and underrepresentation of Bacteroides xylanisolvens and Bifidobacterium longum in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut-brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups. CONCLUSIONS: Levels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder.

260. Interleukin-32 as a biomarker in rheumatic diseases: A narrative review.

Front Immunol

2023 Feb 15

Kwon OC, Park MC, Kim YG.

261. Emergence and competition of virus variants in respiratory viral infections.

Front Immunol

2023 Feb 14

Bessonov N, Neverova D, Popov V

262. The central role of natural killer cells in preeclampsia.

Front Immunol

2023 Feb 14

Wei X, Yang X.

263. Exosome-derived CIRP: An amplifier of inflammatory diseases.

Front Immunol

2023 Feb 14

Han J, Zhang Y, Ge P

264. TNFR2 expression predicts the responses to immune checkpoint inhibitor treatments.

Front Immunol

2023 Feb 14

Liao P, Jiang M, Islam MS

265. Ratio of lymphocyte to monocyte area under the curve as a novel predictive factor for severe infection in multiple sclerosis.

Front Immunol

2023 Feb 14

Takahashi J, Okamoto T, Lin Y

BACKGROUND: Individuals with multiple sclerosis (MS) are vulnerable to all types of infection, because MS itself involves immunodeficiency, in addition to involving treatment with immunosuppressants. Simple predictive variables for infection that are easily assessed in daily examinations are warranted. Lymphocyte area under the curve (L_AUC), defined as the sum of serial absolute lymphocyte counts under the lymphocyte count-time curve, has been established as a predictive factor for several infections after allogenic hematopoietic stem cell transplantation. We assessed whether L_AUC could also be a useful factor for predicting severe infection in MS patients. METHODS: From October 2010 to January 2022, MS patients, diagnosed based on the 2017 McDonald criteria, were retrospectively reviewed. We extracted patients with infection requiring hospitalization (IRH) from medical records and matched with controls in a 1:2 ratio. Variables including clinical severity and laboratory data were compared between the infection group and controls. L_AUC was calculated along with the AUC of total white blood cells (W_AUC), neutrophils (N_AUC), lymphocytes (L_AUC), and monocytes (M_AUC). To correct for different times of blood examination and extract mean values of AUC per time point, we divided the AUC by follow-up duration. For example, in evaluating lymphocyte counts, we defined the ratio of [L_AUC] to [follow-up duration] as [L_AUC/t]. Multivariate regression analysis was conducted to extract predictive factors associated with IRH. Also, discriminative analysis was conducted using candidate variables from multivariate analysis. RESULTS: The total case-control sample included 177 patients of MS with IRH (n=59) and non-IRH (controls) (n=118). Adjusted odds ratios (OR) for the risk of serious infection in patients with MS with higher baseline expanded disability status scale (EDSS) (OR 1.340, 95% confidence interval [CI] 1.070-1.670, p = 0.010) and lower ratio of L_AUC/t to M_AUC/t (OR 0.766, 95%CI 0.591-0.993, p = 0.046) were significant. Notably, the kind of treatment, including glucocorticoids (GCs), disease-modifying drugs (DMDs) and other immunosuppressants agents, and dose of GCs were not significantly associated with serious infection after correlated with EDSS and ratio of L_AUC/t to M_AUC/t. In discriminative analysis, sensitivity was 88.1% (95%CI 76.5-94.7%) and specificity was 35.6% (95%CI 27.1-45.0%), using EDSS ≥ 6.0 or ratio of L_AUC/t to M_AUC/t ≤ 3.699, while sensitivity was 55.9% (95%CI 42.5-68.6%) and specificity was 83.9% (95%CI 75.7-89.8%), using both EDSS ≥ 6.0 and ratio of L_AUC/t to M_AUC/t ≤ 3.699. CONCLUSION: Our study revealed the impact of the ratio L_AUC/t to M_AUC/t as a novel prognostic factor for IRH. Clinicians should pay more attention to laboratory data such as lymphocyte or monocyte counts itself, directly presenting individual immunodeficiency, rather than the kind of drug to prevent infection as a clinical manifestation.

266. Insulin-like growth factor binding protein 5b of Trachinotus ovatus and its heparin-binding motif play a critical role in host antibacterial immune responses via NF-κB pathway.

Front Immunol

2023 Feb 14

Du H, Zhou Y, Du X

INTRODUCTION: Insulin-like growth factor binding protein 5 (IGFBP5) exerts an essential biological role in many processes, including apoptosis, cellular differentiation, growth, and immune responses. However, compared to mammalians, our knowledge of IGFBP5 in teleosts remains limited. METHODS: In this study, TroIGFBP5b, an IGFBP5 homologue from golden pompano (Trachinotus ovatus) was identified. Quantitative real-time PCR (qRT-PCR) was used to check its mRNA expression level in healthy condition and after stimulation. In vivo overexpression and RNAi knockdown method were performed to evaluate the antibacterial profile. We constructed a mutant in which HBM was deleted to better understand the mechanism of its role in antibacterial immunity. Subcellular localization and nuclear translocation were verified by immunoblotting. Further, proliferation of head kidney lymphocytes (HKLs) and phagocytic activity of head kidney macrophages (HKMs) were detected through CCK-8 assay and flow cytometry. Immunofluorescence microscopy assay (IFA) and dual luciferase reporter (DLR) assay were used to evaluate the activity in nuclear factor-κB (NF-κβ) pathway. RESULTS: The TroIGFBP5b mRNA expression level was upregulated after bacterial stimulation. In vivo, TroIGFBP5b overexpression significantly improved the antibacterial immunity of fish. In contrast, TroIGFBP5b knockdown significantly decreased this ability. Subcellular localization results showed that TroIGFBP5b and TroIGFBP5b-δHBM were both present in the cytoplasm of GPS cells. After stimulation, TroIGFBP5b-δHBM lost the ability to transfer from the cytoplasm to the nucleus. In addition, rTroIGFBP5b promoted the proliferation of HKLs and phagocytosis of HKMs, whereas rTroIGFBP5b-δHBM, suppressed these facilitation effects. Moreover, the in vivo antibacterial ability of TroIGFBP5b was suppressed and the effects of promoting expression of proinflammatory cytokines in immune tissues were nearly lost after HBM deletion. Furthermore, TroIGFBP5b induced NF-κβ promoter activity and promoted nuclear translocation of p65, while these effects were inhibited when the HBM was deleted. DISCUSSION: Taken together, our results suggest that TroIGFBP5b plays an important role in golden pompano antibacterial immunity and activation of the NF-κβ signalling pathway, providing the first evidence that the HBM of TroIGFBP5b plays a critical role in these processes in teleosts.

267. An advanced understanding of the heterogeneous clinical features of "non-criteria" obstetric antiphospholipid syndrome: Two case reports and a literature review.

Front Immunol

2023 Feb 14

Peng X, Tan X, Xing A.

268. Macrophage: Key player in the pathogenesis of autoimmune diseases.

Front Immunol

2023 Feb 14

Yang S, Zhao M, Jia S.

269. The interaction between dietary fiber and gut microbiota, and its effect on pig intestinal health.

Front Immunol

2023 Feb 14

Hu R, Li S, Diao H

270. The IgH Eµ-MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation.

Front Immunol

2023 Feb 14

Martin OA, Thomas M, Marquet M

271. Role of chemokine-like factor 1 as an inflammatory marker in diseases.

Front Immunol

2023 Feb 14

Li Y, Yu H, Feng J.

272. Novel exosome-related risk signature as prognostic biomarkers in glioblastoma.

Front Immunol

2023 Feb 14

Ding M, Xu Q, Jin X

273. Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A.

Front Immunol

2023 Feb 14

Panova EA, Kleymenov DA, Shcheblyakov DV

274. Establishment of national standard for anti-SARS-Cov-2 neutralizing antibody in China: The first National Standard calibration traceability to the WHO International Standard.

Front Immunol

2023 Feb 14

Guan L, Mao Q, Tan D

275. Dietary fiber alters immunity and intestinal barrier function of different breeds of growing pigs.

Front Immunol

2023 Feb 14

Ding S, Cheng Y, Azad MAK

INTRODUCTION: Dietary fiber (DF) regulates immune response and barrier function by interacting with epithelial cells and immune cells. However, the differences in the regulation of intestinal health of different pig breeds by DF remain obscure. METHODS: A total of 60 healthy pigs (20 pigs/breed) from Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) pigs (body weight = 11.00 ± 1.00 kg) were fed two different levels (low and high) of DF for 28 days to evaluate the differences in the modulation of intestinal immunity and barrier function by DF in different pig breeds. RESULTS: TB and XB pigs had higher plasma Eos level, Eos%, and Lym% but lower Neu level compared with the DR pigs when fed low DF (LDF). The TB and XB pigs had higher plasma Eos, MCV, and MCH levels and Eos% while lower Neu% compared with the DR pigs when fed high DF (HDF). HDF decreased IgA, IgG, IgM, and sIgA concentrations in the ileum of TB and XB pigs compared with the DR pigs, while the plasma IgG and IgM concentrations of TB pigs were higher than those of the DR pigs. Moreover, compared with the DR pigs, HDF decreased the levels of IL-1β, IL-17, and TGF-β in the plasma, and IL-1β, IL-2, IL-6, IL-10, IL-17, IFN-γ, TGF-β, and TNF-α in the ileum of TB and XB pigs. However, HDF did not affect the mRNA expression of cytokines in the ileum of TB, XB, and DR pigs, while HDF increased the TRAF6 expression of TB pigs compared with the DR pigs. In addition, HDF increased the Claudin abundance of TB and DR pigs compared with the pigs feeding with LDF. Moreover, in the LDF and HDF groups, the XB pigs had higher protein abundances of Claudin and ZO-1 compared with the TB and DR pigs. CONCLUSIONS: DF regulated the TB and DR pigs' plasma immune cells, the XB pigs showed enhanced barrier function, and the DR pigs had increased ileal inflammation, which indicates that Chinese indigenous pigs are more DF tolerant than the DR pigs.

276. Exposure to environmental air pollutants as a risk factor for primary Sjögren's syndrome.

Front Immunol

2023 Feb 14

Ma KS, Wang LT, Chong W

277. Potential effects of shift work on skin autoimmune diseases.

Front Immunol

2023 Feb 14

Stenger S, Grasshoff H, Hundt JE

278. Research progress on the immunomodulatory mechanism of acupuncture in tumor immune microenvironment.

Front Immunol

2023 Feb 14

Wang N, Zhao L, Zhang D

279. Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives.

Front Immunol

2023 Feb 14

Chen S, Liu Y, Zhong Z

280. The immunoregulatory effect of the TREM2-agonist Sulfavant A in human allogeneic mixed lymphocyte reaction.

Front Immunol

2023 Feb 14

Barra G, Gallo C, Carbone D

281. CD4(+) T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV.

Front Immunol

2023 Feb 14

Wanjalla CN, Gabriel CL, Fuseini H

282. Tissue-resident, memory CD8(+) T cells are effective in clearing intestinal Eimeria falciformis reinfection in mice.

Front Immunol

2023 Feb 14

Shi F, Zhang S, Zhang N

283. Integration of Candida albicans-induced single-cell gene expression data and secretory protein concentrations reveal genetic regulators of inflammation.

Front Immunol

2023 Feb 14

Boahen CK, Oelen R, Le K

284. Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer.

Front Immunol

2023 Feb 14

Zhou T, Zhang LY, He JZ

285. Exploring the association and causal effect between white blood cells and psoriasis using large-scale population data.

Front Immunol

2023 Feb 14

Zhou G, Ren X, Tang Z

INTRODUCTION: Psoriasis is a chronic inflammatory disease of the skin. A few studies have shown that psoriasis is an immune-mediated disease in which multiple immune cells play crucial roles. However, the association between circulating immune cells and psoriasis remains elusive. METHODS: To explore the role of circulating immune cells in psoriasis, 361,322 individuals from the UK Biobank (UKB) and 3,971 patients with psoriasis from China were included to investigate the association between white blood cells and psoriasis via an observational study. Genome-wide association studies (GWAS) and Mendelian randomization (MR) were used to evaluate the causal relationship between circulating leukocytes and psoriasis. RESULTS: The risk of psoriasis increased with high levels of monocytes, neutrophils, and eosinophils (relative risks and 95% confidence intervals, respectively: 1.430 (1.291-1.584) for monocytes, 1.527 (1.379-1.692) for neutrophils, and 1.417 (1.294-1.551) for eosinophils). Upon further MR analysis, eosinophils showed a definite causal relationship with psoriasis (odds ratio of inverse-variance weighted: 1.386, 95% confidence intervals: 1.092-1.759) and a positive correlation with the psoriasis area and severity index (PASI) score (P = 6.6 × 10-5). The roles of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) in psoriasis were also assessed. More than 20,000 genetic variations associated with NLR, PLR, and LMR were discovered in a GWAS analysis using the UKB data. Following adjustment for covariates in the observational study, NLR and PLR were shown to be risk factors for psoriasis, whereas LMR was a protective factor. MR results indicated that there was no causal relationship between these three indicators and psoriasis; however, NLR, PLR, and LMR correlated with the PASI score (NLR: rho = 0.244, P = 2.1 × 10-21; PLR: rho = 0.113, P = 1.4 × 10-5; LMR: rho = -0.242, P = 3.5×10-21). DISCUSSION: Our findings revealed an important association between circulating leukocytes and psoriasis, which is instructive for the clinical practice of psoriasis treatment.

286. Clinical application of immune repertoire sequencing in solid organ transplant.

Front Immunol

2023 Feb 14

Wong P, Cina DP, Sherwood KR

BACKGROUND: Measurement of T cell receptor (TCR) or B cell receptor (BCR) gene utilization may be valuable in monitoring the dynamic changes in donor-reactive clonal populations following transplantation and enabling adjustment in therapy to avoid the consequences of excess immune suppression or to prevent rejection with contingent graft damage and to indicate the development of tolerance. OBJECTIVE: We performed a review of current literature to examine research in immune repertoire sequencing in organ transplantation and to assess the feasibility of this technology for clinical application in immune monitoring. METHODS: We searched MEDLINE and PubMed Central for English-language studies published between 2010 and 2021 that examined T cell/B cell repertoire dynamics upon immune activation. Manual filtering of the search results was performed based on relevancy and predefined inclusion criteria. Data were extracted based on study and methodology characteristics. RESULTS: Our initial search yielded 1933 articles of which 37 met the inclusion criteria; 16 of these were kidney transplant studies (43%) and 21 were other or general transplantation studies (57%). The predominant method for repertoire characterization was sequencing the CDR3 region of the TCR β chain. Repertoires of transplant recipients were found to have decreased diversity in both rejectors and non-rejectors when compared to healthy controls. Rejectors and those with opportunistic infections were more likely to have clonal expansion in T or B cell populations. Mixed lymphocyte culture followed by TCR sequencing was used in 6 studies to define an alloreactive repertoire and in specialized transplant settings to track tolerance. CONCLUSION: Methodological approaches to immune repertoire sequencing are becoming established and offer considerable potential as a novel clinical tool for pre- and post-transplant immune monitoring.

287. Donor selection for adoptive immunotherapy with NK cells in AML patients: Comparison between analysis of lytic NK cell clones and phenotypical identification of alloreactive NK cell repertoire.

Front Immunol

2023 Feb 14

Meazza R, Ruggeri L, Guolo F

Natural killer (NK) cell-based adoptive immunotherapy in leukemia patients is an emerging field of interest based on clinical evidence of efficacy and safety. Elderly acute myeloid leukemia (AML) patients have been successfully treated with NK cells from HLA-haploidentical donors, especially when high amounts of alloreactive NK cells were infused. The aim of this study was comparing two approaches to define the size of alloreactive NK cells in haploidentical donors for AML patients recruited in two clinical trials with the acronym "NK-AML" (NCT03955848), and "MRD-NK". The standard methodology was based on the frequency of NK cell clones capable of lysing the related patient-derived cells. The alternative approach consisted of the phenotypic identification of freshly derived NK cells expressing, as inhibitory receptors, only the inhibitory KIR(s) specific for the mismatched KIR-Ligand(s) (HLA-C1, HLA-C2, HLA-Bw4). However, in KIR2DS2+ donors and HLA-C1+ patients, the unavailability of reagents staining only the inhibitory counterpart (KIR2DL2/L3) may lead to an underestimated identification of the alloreactive NK cell subset. Conversely, in the case of HLA-C1 mismatch, the alloreactive NK cell subset could be overestimated due to the ability of KIR2DL2/L3 to recognize with low-affinity also HLA-C2. Especially in this context, the additional exclusion of LIR1-expressing cells might be relevant to refine the size of the alloreactive NK cell subset. We could also associate degranulation assays, using as effector cells IL-2 activated donor peripheral blood mononuclear cells (PBMC) or NK cells upon co-culture with the related patient target cells. The donor alloreactive NK cell subset always displayed the highest functional activity, confirming its identification accuracy by flow cytometry. Despite the phenotypic limitations and considering the proposed corrective actions, a good correlation was shown by the comparison of the two investigated approaches. In addition, the characterization of receptor expression on a fraction of NK cell clones revealed expected but also few unexpected patterns. Thus, in most instances, the quantification of phenotypically defined alloreactive NK cells from PBMC can provide data similar to the analysis of lytic clones, with several advantages, such as a shorter time to achieve the results and, perhaps, higher reproducibility/feasibility in many laboratories.

288. Regulation of innate immune signaling by IRAK proteins.

Front Immunol

2023 Feb 14

Pereira M, Gazzinelli RT.

289. Immune checkpoint molecules in prevention and development of asthma.

Front Immunol

2023 Feb 14

Kanannejad Z, Soleimanian S, Ghahramani Z

290. Interactions of pathogenic Escherichia coli with CEACAMs.

Front Immunol

2023 Feb 14

Sheikh A, Fleckenstein JM.

291. A cause-effect relationship between Graves' disease and the gut microbiome contributes to the thyroid-gut axis: A bidirectional two-sample Mendelian randomization study.

Front Immunol

2023 Feb 14

Cao J, Wang N, Luo Y

292. Epstein-Barr virus DNA seropositivity links distinct tumoral heterogeneity and immune landscape in nasopharyngeal carcinoma.

Front Immunol

2023 Feb 13

Li W, Lv S, Liu G

293. An mRNA mix redirects dendritic cells towards an antiviral program, inducing anticancer cytotoxic stem cell and central memory CD8(+) T cells.

Front Immunol

2023 Feb 13

de Mey W, Locy H, De Ridder K

294. Chemokines and chemokine receptors as promising targets in rheumatoid arthritis.

Front Immunol

2023 Feb 13

Murayama MA, Shimizu J, Miyabe C

295. The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage.

Front Immunol

2023 Feb 13

Wang RH, Wen WX, Jiang ZP

BACKGROUND: Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia. METHODS: Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis. RESULTS: A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147). CONCLUSIONS: Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

296. Association between inflammatory cytokines and symptoms of major depressive disorder in adults.

Front Immunol

2023 Feb 13

Min X, Wang G, Cui Y

297. Therapeutic targeting of HCMV-encoded chemokine receptor US28: Progress and challenges.

Front Immunol

2023 Feb 13

Berg C, Rosenkilde MM.

298. Persistent memory despite rapid contraction of circulating T Cell responses to SARS-CoV-2 mRNA vaccination.

Front Immunol

2023 Feb 13

Taus E, Hofmann C, Ibarrondo FJ

INTRODUCTION: While antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined. METHODS: Interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD). RESULTS: In two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination. DISCUSSION: Overall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

299. Physical activity as a promising alternative for young people with juvenile idiopathic arthritis: Towards an evidence-based prescription.

Front Immunol

2023 Feb 13

Rochette E, Saidi O, Merlin É

300. Preventive effects of Mycobacterium tuberculosis DNA vaccines on the mouse model with latent tuberculosis infection.

Front Immunol

2023 Feb 13

Liang Y, Li X, Yang Y

BACKGROUND: About a quarter of the world's population with latent tuberculosis infection (LTBI) are the main source of active tuberculosis. Bacillus Calmette Guerin (BCG) cannot effectively control LTBI individuals from developing diseases. Latency-related antigens can induce T lymphocytes of LTBI individuals to produce higher IFN-γ levels than tuberculosis patients and normal subjects. Herein, we firstly compared the effects of M. tuberculosis (MTB) ag85ab and 7 latent DNA vaccines on clearing latent MTB and preventing its activation in the mouse LTBI model. METHODS: A mouse LTBI model was established, and then immunized respectively with PBS, pVAX1 vector, Vaccae vaccine, ag85ab DNA and 7 kinds of latent DNAs (including rv1733c, rv2660c, rv1813c, rv2029c, rv2628, rv2659c and rv3407) for three times. The mice with LTBI were injected with hydroprednisone to activate the latent MTB. Then, the mice were sacrificed for the bacterial count, histopathological examination, and immunological evaluation. RESULTS: Using chemotherapy made the MTB latent in the infected mice, and then using hormone treatment reactivated the latent MTB, indicating that the mouse LTBI model was successfully established. After the mouse LTBI model was immunized with the vaccines, the lung colony-forming units (CFUs) and lesion degree of mice in all vaccines group were significantly decreased than those in the PBS group and vector group (P<0.0001, P<0.05). These vaccines could induce antigen-specific cellular immune responses. The number of IFN-γ effector T cells spots secreted by spleen lymphocytes in the ag85ab DNA group was significantly increased than those in the control groups (P<0.05). In the splenocyte culture supernatant, IFN-γ and IL-2 levels in the ag85ab, rv2029c, and rv2659c DNA groups significantly increased (P<0.05), and IL-17A levels in ag85ab and rv2659c DNA groups also significantly increased (P<0.05). Compared with the PBS and vector groups, the proportion of CD4+CD25+FOXP3+ regulatory T cells in spleen lymphocytes of ag85ab, rv2660c, rv2029c, and rv3407 DNA groups were significantly reduced (P<0.05). CONCLUSIONS: MTB ag85ab and 7 kinds of latent DNA vaccines showed immune preventive efficacies on a mouse model of LTBI, especially the rv2659c, and rv1733c DNA. Our findings will provide candidates for the development of new multi-stage vaccines against TB.

301. Positive faecal immunochemical test predicts the onset of inflammatory bowel disease: A nationwide, propensity score-matched study.

Front Immunol

2023 Feb 13

Lee E, Lee GH, Park B

302. Research into the characteristic molecules significantly affecting liver cancer immunotherapy.

Front Immunol

2023 Feb 13

Chen J, Jin H, Zhou H

BACKGROUND: The past decade has witnessed unprecedented scientific breakthroughs, including immunotherapy, which has great potential in clinical applications for liver cancer. METHODS: Public data were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases and analyzed with R software. RESULTS: The LASSO and SVM-RFE machine learning algorithms identified 16 differentially expressed genes (DEGs) related to immunotherapy, namely, GNG8, MYH1, CHRNA3, DPEP1, PRSS35, CKMT1B, CNKSR1, C14orf180, POU3F1, SAG, POU2AF1, IGFBPL1, CDCA7, ZNF492, ZDHHC22, and SFRP2. Moreover, a logistic model (CombinedScore) was established based on these DEGs, showing an excellent prediction performance for liver cancer immunotherapy. Patients with a low CombinedScore might respond better to immunotherapy. Gene Set Enrichment Analysis showed that many metabolism pathways were activated in patients with a high CombinedScore, including butanoate metabolism, bile acid metabolism, fatty acid metabolism, glycine serine and threonine metabolism, and propanoate metabolism. Our comprehensive analysis showed that the CombinedScore was negatively correlated with the levels of most tumor-infiltrating immune cells and the activities of key steps of cancer immunity cycles. Continually, the CombinedScore was negatively associated with the expression of most immune checkpoints and immunotherapy response-related pathways. Moreover, patients with a high and a low CombinedScore exhibited diverse genomic features. Furthermore, we found that CDCA7 was significantly correlated with patient survival. Further analysis showed that CDCA7 was positively associated with M0 macrophages and negatively associated with M2 macrophages, suggesting that CDCA7 could influence the progression of liver cancer cells by affecting macrophage polarization. Next, single-cell analysis showed that CDCA7 was mainly expressed in prolif T cells. Immunohistochemical results confirmed that the staining intensity of CDCA7 was prominently increased in the nucleus in primary liver cancer tissues compared to adjacent non-tumor tissues. CONCLUSIONS: Our results provide novel insights into the DEGs and factors affecting liver cancer immunotherapy. Meanwhile, CDCA7 was identified as a potential therapeutic target in this patient population.

303. C. elegans orphan nuclear receptor NHR-42 represses innate immunity and promotes lipid loss downstream of HLH-30/TFEB.

Front Immunol

2023 Feb 13

Goswamy D, Gonzalez X, Labed SA

304. Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors.

Front Immunol

2023 Feb 13

Schepisi G, Gianni C, Cursano MC

305. Alterations in the immune system persist after one year of convalescence in severe COVID-19 patients.

Front Immunol

2023 Feb 13

Abarca-Zabalía J, González-Jiménez A, Calle-Rubio M

306. Exploring the role of sphingolipid-related genes in clinical outcomes of breast cancer.

Front Immunol

2023 Feb 13

Pei S, Zhang P, Yang L

BACKGROUND: Despite tremendous advances in cancer research, breast cancer (BC) remains a major health concern and is the most common cancer affecting women worldwide. Breast cancer is a highly heterogeneous cancer with potentially aggressive and complex biology, and precision treatment for specific subtypes may improve survival in breast cancer patients. Sphingolipids are important components of lipids that play a key role in the growth and death of tumor cells and are increasingly the subject of new anti-cancer therapies. Key enzymes and intermediates of sphingolipid metabolism (SM) play an important role in regulating tumor cells and further influencing clinical prognosis. METHODS: We downloaded BC data from the TCGA database and GEO database, on which we performed in depth single-cell sequencing analysis (scRNA-seq), weighted co-expression network analysis, and transcriptome differential expression analysis. Then seven sphingolipid-related genes (SRGs) were identified using Cox regression, least absolute shrinkage, and selection operator (Lasso) regression analysis to construct a prognostic model for BC patients. Finally, the expression and function of the key gene PGK1 in the model were verified by in vitro experiments. RESULTS: This prognostic model allows for the classification of BC patients into high-risk and low-risk groups, with a statistically significant difference in survival time between the two groups. The model is also able to show high prediction accuracy in both internal and external validation sets. After further analysis of the immune microenvironment and immunotherapy, it was found that this risk grouping could be used as a guide for the immunotherapy of BC. The proliferation, migration, and invasive ability of MDA-MB-231 and MCF-7 cell lines were dramatically reduced after knocking down the key gene PGK1 in the model through cellular experiments. CONCLUSION: This study suggests that prognostic features based on genes related to SM are associated with clinical outcomes, tumor progression, and immune alterations in BC patients. Our findings may provide insights for the development of new strategies for early intervention and prognostic prediction in BC.

307. IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression.

Front Immunol

2023 Feb 13

Bhattarai U, He X, Xu R

308. Phase separation in innate immune response and inflammation-related diseases.

Front Immunol

2023 Feb 13

Ma H, Liu M, Fu R

309. Immunosuppressive capacity of circulating MDSC predicts response to immune checkpoint inhibitors in melanoma patients.

Front Immunol

2023 Feb 13

Petrova V, Groth C, Bitsch R

310. Case Report: Nontuberculous mycobacterial infections in children with complete DiGeorge anomaly.

Front Immunol

2023 Feb 13

Hicks ED, Agada NO, Yates TR

311. Mendelian randomization study shows a causal effect of asthma on epilepsy risk.

Front Immunol

2023 Feb 13

Tang P, Guo X, Chong L

312. Predictive value of (18)F-FDG PET/CT for evaluating the response to hypofractionated radiotherapy combined with PD-1 blockade in non-small cell lung cancer.

Front Immunol

2023 Feb 13

Tang S, Zhang Y, Li Y

313. Heterologous prime-boost cellular vaccination induces potent antitumor immunity against triple negative breast cancer.

Front Immunol

2023 Feb 13

Niavarani SR, St-Cyr G, Daniel L

INTRODUCTION: Triple negative breast cancer (TNBC) is the most aggressive and hard-to-treat subtype of breast cancer, affecting 10-20% of all women diagnosed with breast cancer. Surgery, chemotherapy and hormone/Her2 targeted therapies are the cornerstones of treatment for breast cancer, but women with TNBC do not benefit from these treatments. Although the prognosis is dismal, immunotherapies hold significant promise in TNBC, even in wide spread disease because TNBC is infiltrated with more immune cells. This preclinical study is proposing to optimize an oncolytic virus-infected cell vaccine (ICV) based on a prime-boost vaccination strategy to address this unmet clinical need. METHODS: We used various classes of immunomodulators to improve the immunogenicity of whole tumor cells in the prime vaccine, followed by their infection with oncolytic Vesicular Stomatitis Virus (VSVd51) to deliver the boost vaccine. For in vivo studies, we compared the efficacy of a homologous prime-boost vaccination regimen to a heterologous strategy by treating 4T1 tumor bearing BALB/c mice and further by conducting re-challenge studies to evaluate immune memory responses in surviving mice. Due to the aggressive nature of 4T1 tumor spread (akin to stage IV TNBC in human patients), we also compared early surgical resection of primary tumors versus later surgical resection combined with vaccination. RESULTS: In vitro results demonstrated that immunogenic cell death (ICD) markers and pro-inflammatory cytokines were released at the highest levels following treatment of mouse 4T1 TNBC cells with oxaliplatin chemotherapy and influenza vaccine. These ICD inducers also contributed towards higher dendritic cell recruitment and activation. With the top ICD inducers at hand, we observed that treatment of TNBC-bearing mice with the influenza virus-modified prime vaccine followed by VSVd51 infected boost vaccine resulted in the best survival. Furthermore, higher frequencies of both effector and central memory T cells along with a complete absence of recurrent tumors were observed in re-challenged mice. Importantly, early surgical resection combined with prime-boost vaccination led to improved overall survival in mice. CONCLUSION: Taken together, this novel cancer vaccination strategy following early surgical resection could be a promising therapeutic avenue for TNBC patients.

314. Identification of shared gene signatures and molecular mechanisms between chronic kidney disease and ulcerative colitis.

Front Immunol

2023 Feb 13

Liang Z, Hu X, Lin R

BACKGROUND: There is a complex interaction between chronic kidney disease (CKD) and ulcerative colitis (UC), but the pathophysiological mechanisms underlying the coexistence of CKD and UC are unclear. This study aimed to investigate the key molecules and pathways that may mediate the co-occurrence of CKD and UC through quantitative bioinformatics analysis based on a public RNA-sequencing database. METHODS: The discovery datasets of CKD (GSE66494) and UC (GSE4183), as well as validation datasets of CKD (GSE115857) and UC (GSE10616), were downloaded from the Gene Expression Omnibus (GEO) database. After identifying differentially expressed genes (DEGs) with GEO2R online tool, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for the DEGs were performed. Next, protein-protein interaction network was constructed with Search Tool for the Retrieval of Interacting Genes (STRING) and visualized by Cytoscape. Gene modules were identified by the plug-in MCODE and hub genes were screened using the plug-in CytoHubba. Then, correlation between immune cell infiltration and hub genes was analyzed, and the receiver operating characteristic curves were used to assess the predictive value of hub genes. Finally, immunostaining of human specimens was used to validate the relevant findings. RESULTS: A total of 462 common DEGs were identified and selected for further analyses. GO and KEGG enrichment analyses indicated that these DEGs were primarily enriched in immune- and inflammation-related pathways. Among them, the PI3K-Akt signaling pathway ranked top in both discovery and validation cohorts, and the key signal molecule phosphorylated Akt (p-Akt) was shown to be significantly overexpressed in human CKD kidneys and UC colons, and further elevated in CKD-UC comorbidity specimens. Moreover, nine candidate hub genes, including CXCL8, CCL2, CD44, ICAM1, IL1A, CXCR2, PTPRC, ITGAX, and CSF3, were identified, of which ICAM1 was validated as a common hub gene. Besides, immune infiltration analysis revealed that neutrophils, macrophages, and CD4+ T memory cells significantly accumulated in both diseases, and ICAM1 was remarkably associated with neutrophil infiltration. Furthermore, intercellular adhesion molecule1 (ICAM1)-mediated neutrophil infiltration was validated to be upregulated in kidney and colon biopsies of CKD and UC patients, and further increased in patients diagnosed with both CKD and UC. Finally, ICAM1 had shown critical value as a diagnostic marker for the co-occurrence of CKD and UC. CONCLUSIONS: Our study elucidated that immune response, PI3K-Akt signaling pathway, and ICAM1-mediated neutrophil infiltration might be the common pathogenesis of CKD and UC, and identified ICAM1 as a key potential biomarker and therapeutic target for the comorbidity of these two diseases.

315. Modulation by luminal factors on the functions and migration of intestinal innate immunity.

Front Immunol

2023 Feb 13

Higashiyama M, Miura S, Hokari R.

316. Cell morphology as a biological fingerprint of chondrocyte phenotype in control and inflammatory conditions.

Front Immunol

2023 Feb 13

Selig M, Azizi S, Walz K

INTRODUCTION: Little is known how inflammatory processes quantitatively affect chondrocyte morphology and how single cell morphometric data could be used as a biological fingerprint of phenotype. METHODS: We investigated whether trainable high-throughput quantitative single cell morphology profiling combined with population-based gene expression analysis can be used to identify biological fingerprints that are discriminatory of control vs. inflammatory phenotypes. The shape of a large number of chondrocytes isolated from bovine healthy and human osteoarthritic (OA) cartilages was quantified under control and inflammatory (IL-1β) conditions using a trainable image analysis technique measuring a panel of cell shape descriptors (area, length, width, circularity, aspect ratio, roundness, solidity). The expression profiles of phenotypically relevant markers were quantified by ddPCR. Statistical analysis, multivariate data exploration, and projection-based modelling were used for identifying specific morphological fingerprints indicative of phenotype. RESULTS: Cell morphology was sensitive to both cell density and IL-1β. In both cell types, all shape descriptors correlated with expression of extracellular matrix (ECM)- and inflammatory-regulating genes. A hierarchical clustered image map revealed that individual samples sometimes responded differently in control or IL-1β conditions than the overall population. Despite these variances, discriminative projection-based modeling revealed distinct morphological fingerprints that discriminated between control and inflammatory chondrocyte phenotypes: the most essential morphological characteristics attributable to non-treated control cells was a higher cell aspect ratio in healthy bovine chondrocytes and roundness in OA human chondrocytes. In contrast, a higher circularity and width in healthy bovine chondrocytes and length and area in OA human chondrocytes indicated an inflammatory (IL-1β) phenotype. When comparing the two species/health conditions, bovine healthy and human OA chondrocytes exhibited comparable IL-1β-induced morphologies in roundness, a widely recognized marker of chondrocyte phenotype, and aspect ratio. DISCUSSION: Overall, cell morphology can be used as a biological fingerprint for describing chondrocyte phenotype. Quantitative single cell morphometry in conjunction with advanced methods for multivariate data analysis allows identifying morphological fingerprints that can discriminate between control and inflammatory chondrocyte phenotypes. This approach could be used to assess how culture conditions, inflammatory mediators, and therapeutic modulators regulate cell phenotype and function.

317. Systemic inflammatory markers in patients with polyneuropathies.

Front Immunol

2023 Feb 13

García-Fernández P, Höfflin K, Rausch A

318. An immune genes signature for predicting mortality in sepsis patients.

Front Immunol

2023 Feb 13

Lin S, Li P, Yang J

319. Systemic lupus erythematosus is causally associated with hypothyroidism, but not hyperthyroidism: A Mendelian randomization study.

Front Immunol

2023 Feb 13

Qin Q, Zhao L, Ren A

BACKGROUND: The relationship between systemic lupus erythematosus (SLE) and thyroid diseases is still controversial. Due to confounders and reverse causation, previous studies were not convincing. We aimed to investigate the relationship between SLE and hyperthyroidism or hypothyroidism by Mendelian randomization (MR) analysis. METHODS: We performed a two-step analysis using bidirectional two-sample univariable and multivariable MR (MVMR) to explore the causality of SLE and hyperthyroidism or hypothyroidism in three genome-wide association studies (GWAS) datasets, including 402,195 samples and 39,831,813 single-nucleotide polymorphisms (SNPs). In the first step analysis, with SLE as exposure and thyroid diseases as outcomes, 38 and 37 independent SNPs strongly (P < 5*10-8) associated with SLE on hyperthyroidism or SLE on hypothyroidism were extracted as valid instrumental variables (IVs). In the second step analysis, with thyroid diseases as exposures and SLE as outcome, 5 and 37 independent SNPs strongly associated with hyperthyroidism on SLE or hypothyroidism on SLE were extracted as valid IVs. In addition, MVMR analysis was performed in the second step analysis to eliminate the interference of SNPs that were strongly associated with both hyperthyroidism and hypothyroidism. 2 and 35 valid IVs for hyperthyroidism on SLE and hypothyroidism on SLE were obtained in MVMR analysis. MR results of two steps analysis were estimated respectively by multiplicative random effects-inverse variance weighted (MRE-IVW), simple mode (SM), weighted median (WME) and MR-Egger regression methods. Sensitivity analysis and visualization of MR results were performed by heterogeneity test, pleiotropy test, leave-one-out test, scatter plots, forest plots and funnel plots. RESULTS: The MRE-IVW method in the first step of MR analysis revealed that SLE was causally associated with hypothyroidism (OR = 1.049, 95% CI = 1.020-1.079, P < 0.001), but not causally associated with hyperthyroidism (OR = 1.045, 95% CI = 0.987-1.107, P = 0.130). In the inverse MR analysis, the MRE-IVW method revealed that both hyperthyroidism (OR = 1.920, 95% CI = 1.310-2.814, P < 0.001) and hypothyroidism (OR = 1.630, 95% CI = 1.125-2.362, P = 0.010) were causally associated with SLE. Results from other MR methods were consistent with MRE-IVW. However, when MVMR analysis was performed, there was no longer a causal relationship of hyperthyroidism on SLE (OR = 1.395, 95% CI = 0.984-1.978, P = 0.061), nor was there a causal relationship of hypothyroidism on SLE (OR = 1.290, 95% CI = 0.823-2.022, P = 0.266). The stability and reliability of the results were confirmed by sensitivity analysis and visualization. CONCLUSIONS: Our univariable and multivariable MR analysis revealed that systemic lupus erythematosus was causally associated with hypothyroidism, but did not provided evidence to support a causal relationship of hypothyroidism on SLE or between SLE and hyperthyroidism.

320. An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway.

Front Immunol

2023 Feb 13

Trezise S, Kong IY, Hawkins ED

321. Hydrogen peroxide attenuates rhinovirus-induced anti-viral interferon secretion in sinonasal epithelial cells.

Front Immunol

2023 Feb 13

Lee SH, Han MS, Lee TH

322. Risk of hospitalization and vaccine effectiveness among COVID-19 patients in the UAE during the Delta and Omicron outbreaks.

Front Immunol

2023 Feb 13

Albreiki M, Mousa M, Azman SK

323. Advances in preventive vaccine development against HTLV-1 infection: A systematic review of the last 35 years.

Front Immunol

2023 Feb 13

Santana CS, Andrade FO, da Silva GCS

324. Lipid metabolism-related gene signature predicts prognosis and depicts tumor microenvironment immune landscape in gliomas.

Front Immunol

2023 Feb 13

Li J, Zhang S, Chen S

BACKGROUND: Glioma is the most common primary brain tumor in adults and accounts for more than 70% of brain malignancies. Lipids are crucial components of biological membranes and other structures in cells. Accumulating evidence has supported the role of lipid metabolism in reshaping the tumor immune microenvironment (TME). However, the relationship between the immune TME of glioma and lipid metabolism remain poorly described. MATERIALS AND METHODS: The RNA-seq data and clinicopathological information of primary glioma patients were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). An independent RNA-seq dataset from the West China Hospital (WCH) also included in the study. Univariate Cox regression and LASSO Cox regression model was first to determine the prognostic gene signature from lipid metabolism-related genes (LMRGs). Then a risk score named LMRGs-related risk score (LRS) was established and patients were stratified into high and low risk groups according to LRS. The prognostic value of the LRS was further demonstrated by construction of a glioma risk nomogram. ESTIMATE and CIBERSORTx were used to depicted the TME immune landscape. Tumor Immune Dysfunction and Exclusion (TIDE) was utilized to predict the therapeutic response of immune checkpoint blockades (ICB) among glioma patients. RESULTS: A total of 144 LMRGs were differentially expressed between gliomas and brain tissue. Finally, 11 prognostic LMRGs were included in the construction of LRS. The LRS was demonstrated to be an independent prognostic predictor for glioma patients, and a nomogram consisting of the LRS, IDH mutational status, WHO grade, and radiotherapy showed a C-index of 0.852. LRS values were significantly associated with stromal score, immune score, and ESTIMATE score. CIBERSORTx indicated remarkable differences in the abundance of TME immune cells between patients with high and low LRS risk levels. Based on the results of TIDE algorithm, we speculated that the high-risk group had a greater chance of benefiting from immunotherapy. CONCLUSION: The risk model based upon LMRGs could effectively predict prognosis in patients with glioma. Risk score also divided glioma patients into different groups with distinct TME immune characteristics. Immunotherapy is potentially beneficial to glioma patients with certain lipid metabolism profiles.

325. Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells.

Front Immunol

2023 Feb 13

Liu X, Wei Q, Lu L

Newmer生物

Newmer生物