Cytokines in autoimmunity: role in induction, regulation, and treatment

Abstract

Cytokines play a pivotal role in the pathogenesis of autoimmune diseases. The precise triggers for the breakdown of self-tolerance and the subsequent events leading to the induction of pathogenic autoimmune responses remain to be defined for most of the naturally occurring autoimmune diseases. Studies conducted in experimental models of human autoimmune diseases and observations in patients have revealed a general scheme in which proinflammatory cytokines contribute to the initiation and propagation of autoimmune inflammation, whereas anti-inflammatory cytokines facilitate the regression of inflammation and recovery from acute phase of the disease. This idea is embodied in the T helper (Th) 1/Th2 paradigm, which over the past two decades has had a major influence on our thinking about the role of cytokines in autoimmunity. Interestingly, over the past decade, the interleukin (IL)-17/IL-23 axis has rapidly emerged as the new paradigm that has compelled us to critically re-examine the cytokine-driven immune events in the pathogenesis and treatment of autoimmunity. In this 2-volume special issue of the journal, leading experts have presented their research findings and viewpoints on the role of cytokines in the context of specific autoimmune diseases.

FIG. 1.

The involvement of different T cell subsets and the cytokines produced by them in the pathogenesis of autoimmune disorders. There are diverse subsets of effector and regulatory T cells, and the balance in their activity is vital for an effective immune response that is proportionate to the inciting stimulus. Excessive, reduced, or aberrant cytokine responses contribute significantly to autoimmune inflammation that underlies several autoimmune diseases. T helper 1 (Th1), Th17, Th22, and Th9 subsets (left panel) generally drive pathogenic effector responses, whereas Th2, CD4+CD25+ forkhead box p 3 (Foxp3)+ T regulatory cell (Treg), interleukin (IL)-10-secreting regulatory T cell (Tr1), and transforming growth factor (TGF)-β-secreting T cell (Th3) subsets (right panel) mediate regulatory responses. T follicular helper cell (TfH) is a recently described T cell subset that plays a role in B cell activation in the lymphoid tissue. The primary cytokines secreted by various T cell subsets are shown in the figure. Also depicted are the properties displayed by various T cell subsets and/or cytokines (middle panel) that come into play at different stages of an autoimmune disease.