IL-17 and IL-17-producing cells in protection versus pathology
- Nat Rev Immunol. 2023 Jan;23(1):38-54. doi: 10.1038/s41577-022-00746-9.
- 1. School of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin, Ireland. [email protected].
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.