ADAR1 and ZBP1 are the only two mammalian proteins that contain Zα domains, which are thought to bind to nucleic acids in the Z-conformation. These two molecules are crucial in regulating diverse biological processes. While ADAR1-mediated RNA editing supports host survival and development, ZBP1-mediated immune responses provide host defense against infection and disease. Recent studies have expanded our understanding of the functions of ADAR1 and ZBP1 beyond their classical roles and established their fundamental regulation of innate immune responses, including NLRP3 inflammasome activation, inflammation, and cell death. Their roles in these processes have physiological impacts across development, infectious and inflammatory diseases, and cancer. In this review, we discuss the functions of ADAR1 and ZBP1 in regulating innate immune responses in development and disease.

Obesity is associated with the development of various complications, including diabetes, atherosclerosis, and an increased risk for infections, driven by dysfunctional innate immune responses. Recent insights have revealed that the availability of nutrients is a key determinant of innate immune cell function. Although the presence of obesity is associated with overnutrition of macronutrients, several micronutrient-deficiencies, including Vitamin D and zinc, are often present. Micronutrients have been attributed important immunomodulatory roles. In this review, we summarize current knowledge of the immunomodulatory effects of Vitamin D and zinc. We also suggest future lines of research to further improve our understanding of these micronutrients; this may serve as a stepping-stone to explore micronutrient supplementation to improve innate immune cell function during obesity.

The etiology of most autoimmune diseases remains unknown; however, shared among them is a disruption of immunoregulation. Prostaglandin lipid signaling molecules possess context-dependent immunoregulatory properties, making their role in autoimmunity difficult to decipher. For example, prostaglandin E2 (PGE2) can function as an immunosuppressive molecule as well as a proinflammatory mediator in different circumstances, contributing to the expansion and activation of T cell subsets associated with autoimmunity. Recently, PGE2 was shown to play important roles in the resolution and post-resolution phases of inflammation, promoting return to tissue homeostasis. We propose that PGE2 plays both proinflammatory and pro-resolutory roles in the etiology of autoimmunity, and that harnessing this signaling pathway during the resolution phase might help prevent autoimmune attack.

Vaccines have dramatically changed the COVID-19 pandemic. Over 30 vaccines that were developed on four main platforms are currently being used globally, but a deep dissection of the immunological mechanisms by which they operate is limited to only a few of them. Here, we review the evidence describing specific aspects of the modes of action of COVID-19 vaccines; these include innate immunity, trained innate immunity, and mucosal responses. We also discuss the use of COVID-19 vaccines in the African continent which is ridden with inequality in its access to vaccines and vaccine-related immunological research. We argue that strengthening immunology research in Africa should inform on fundamental aspects of vaccination, including the relevance of genetics, trained innate immunity, and microbiome diversity.