Search

Summary: The immune system plays a critical role in protecting the host against infection but is subject to numerous levels of control that are necessary to prevent pathological, tissue-damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms, or environmental antigens can lead to chronic, debilitating, and degenerative diseases. Regulatory T cells have an essential, non-redundant, and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells. In addition to controlling immune responses, there is a growing understanding that regulatory T cells also contribute directly to tissue homeostasis by promoting tissue regeneration and repair. For these reasons, the prospect of enhancing regulatory T-cell numbers and/or function in patients represents an appealing therapeutic opportunity with potential applications in many diseases, including some where the pathological role of the immune system has only recently been recognized. Approaches to enhance regulatory T cells are now starting to be explored in clinical studies in humans. This review series brings together papers highlighting the Treg-enhancing approaches that are most advanced clinically and examples of therapeutic opportunities based on our growing understanding of regulatory T-cell functions. [ABSTRACT FROM AUTHOR]

Transgenic mice expressing human major histocompatibility complex class II (MHCII) risk alleles are widely used in autoimmune disease research, but limitations arise due to non‐physiologic expression. To address this, physiologically relevant mouse models are established via knock‐in technology to explore the role of MHCII in diseases like rheumatoid arthritis. The gene sequences encoding the ectodomains are replaced with the human DRB1*04:01 and 04:02 alleles, DRA, and CD74 (invariant chain) in C57BL/6N mice. The collagen type II (Col2a1) gene is modified to mimic human COL2. Importantly, DRB1*04:01 knock‐in mice display physiologic expression of human MHCII also on thymic epithelial cells, in contrast to DRB1*04:01 transgenic mice. Humanization of the invariant chain enhances MHCII expression on thymic epithelial cells, increases mature B cell numbers in spleen, and improves antigen presentation. To validate its functionality, the collagen‐induced arthritis (CIA) model is used, where DRB1*04:01 expression led to a higher susceptibility to arthritis, as compared with mice expressing DRB1*04:02. In addition, the humanized T cell epitope on COL2 allows autoreactive T cell‐mediated arthritis development. In conclusion, the humanized knock‐in mouse faithfully expresses MHCII, confirming the DRB1*04:01 alleles role in rheumatoid arthritis and being also useful for studying MHCII‐associated diseases. [ABSTRACT FROM AUTHOR]

CD4+ T cells play a critical role in the pathogenesis of viral diseases, which are activated by the internal metabolic pathways encountering with viral antigens. Glutaminolysis converts glutamine into tricarboxylic acid (TCA) circulating metabolites by α-ketoglutaric acid, which is essential for the proliferation and differentiation of CD4+ T cells and plays a central role in providing the energy and structural components needed for viral replication after the virus hijacks the host cell. Changes in glutaminolysis in CD4+ T cells are accompanied by changes in the viral status of the host cell due to competition for glutamine between immune cells and host cells. More recently, attempts have been made to treat tumours, autoimmune diseases, and viral diseases by altering the breakdown of glutamine in T cells. In this review, we will discuss the current knowledge of glutaminolysis in the CD4+ T cell subsets from viral diseases, not only increasing our understanding of immunometabolism but also providing a new perspective for therapeutic target in viral diseases. [ABSTRACT FROM AUTHOR]

B cells are classically considered solely as antibody-producing cells driving humoral immune responses to foreign antigens in infections and vaccinations as well as self-antigens in pathological settings such as autoimmunity. However, it has now become clear that B cells can also secrete a vast array of cytokines, which influence both pro- and anti-inflammatory immune responses. Indeed, similarly to T cells, there is significant heterogeneity in cytokine-driven responses by B cells, ranging from the production of pro-inflammatory effector cytokines such as IL-6, through to the release of immunosuppressive cytokines such as IL-10. In this review, focusing on human B cells, we summarize the key findings that have revealed that cytokine-producing B cell subsets have critical functions in healthy immune responses and contribute to the pathophysiology of autoimmune diseases. B cells are classically considered solely as antibody-producing cells driving humoral immune responses to foreign antigens in infections and vaccinations as well as self-antigens in pathological settings such as autoimmunity. However, it has now become clear that B cells can also secrete a vast array of cytokines, which influence both pro- and anti-inflammatory immune responses. In this review, focusing on human B cells, we summarise the key findings that have revealed that cytokine-producing B cell subsets have critical functions in healthy immune responses and contribute to the pathophysiology of autoimmune diseases. [ABSTRACT FROM AUTHOR]