IL-17 and IL-17-producing cells in protection versus pathology

IL-17 cytokine family members have diverse biological functions, promoting protective immunity against many pathogens but also driving inflammatory pathology during infection and autoimmunity. IL-17A and IL-17F are produced by CD4+ and CD8+ T cells, γδ T cells, and various innate immune cell populations in response to IL-1β and IL-23, and they mediate protective immunity against fungi and bacteria by promoting neutrophil recruitment, antimicrobial peptide production and enhanced barrier function. IL-17-driven inflammation is normally controlled by regulatory T cells and the anti-inflammatory cytokines IL-10, TGFβ and IL-35. However, if dysregulated, IL-17 responses can promote immunopathology in the context of infection or autoimmunity. Moreover, IL-17 has been implicated in the pathogenesis of many other disorders with an inflammatory basis, including cardiovascular and neurological diseases. Consequently, the IL-17 pathway is now a key drug target in many autoimmune and chronic inflammatory disorders; therapeutic monoclonal antibodies targeting IL-17A, both IL-17A and IL-17F, the IL-17 receptor, or IL-23 are highly effective in some of these diseases. However, new approaches are needed to specifically regulate IL-17-mediated immunopathology in chronic inflammation and autoimmunity without compromising protective immunity to infection. IL-17 cytokines drive biological responses that protect the host against many infections but can also contribute to host pathology in the context of infection and autoimmunity. Here, Kingston Mills highlights the different cellular sources of IL-17 and compares the pathological versus protective functions of these cytokines.