Induction, function and regulation of IL-17-producing T cells

Recent reports have provided convincing evidence that IL‐17‐producing T cells play a key role in the pathogenesis of organ‐specific autoimmune diseases, a function previously attributed exclusively to IFN‐γ‐secreting Th1 cells. Furthermore, it appears that IL‐17‐producing T cells can also function with Th1 cells to mediate protective immunity to pathogens. Although much of the focus has been on IL‐17‐secreting CD4⁺ T cells, termed Th17 cells, CD8⁺ T cells, γδ T cells and NKT cells are also capable of secreting IL‐17. The differentiation of Th17 cells from naïve T cells appears to involve signals from TGF‐β, IL‐6, IL‐21, IL‐1β and IL‐23. Furthermore, IL‐1α or IL‐1β in synergy with IL‐23 can promote IL‐17 secretion from memory T cells. The induction or function of Th17 cells is regulated by cytokines secreted by the other major subtypes of T cells, including IFN‐γ, IL‐4, IL‐10 and at high concentrations, TGF‐β. The main function of IL‐17‐secreting T cells is to mediate inflammation, by stimulating production of inflammatory cytokines, such as TNF‐α, IL‐1β and IL‐6, and inflammatory chemokines that promote the recruitment of neutrophils and macrophages.