IL-17-producing γδ T cells and innate lymphoid cells

The inflammatory cytokine IL-17 plays a critical role in immunity to infection and is involved in the inflammatory pathology associated with certain autoimmune diseases, such as psoriasis and rheumatoid arthritis. While CD4+ and CD8+ T cells are important sources of this cytokine, recent evidence has suggested that ?d T cells and a number of families of innate lymphoid cells (ILCs) can secrete IL-17 and related cytokines. The production of IL-17 by ?d T cells appears to be largely independent of T-cell receptor act-ivation and is promoted through cytokine signalling, in particular by IL-23 in combination with IL-1 beta or IL-18. Therefore IL-17-secreting ?d T cells can be categorised as a family of cells similar to innate-like lymphoid cells. IL-17-secreting ?d T cells function as a part of mucosal defence against infection, with most studies to date focusing on their response to bacterial pathogens. ?d T cells also play a pathological role in certain autoimmune diseases, where they provide an early source of IL-17 and IL-21, which initiate responses mediated by conventional IL-17-secreting CD4+ T cells (Th17 cells). ILCs lack an antigen receptor or other linage markers, and ILC subsets that express the transcriptional factor ROR?t have been found to secrete IL-17. Evidence is emerging that these newly recognised sources of IL-17 play both pathological and protective roles in inflammatory diseases as discussed in this article.