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

Abstract

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 γδ 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 γδ 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‐1β or IL‐18. Therefore IL‐17‐secreting γδ T cells can be categorised as a family of cells similar to innate‐like lymphoid cells. IL‐17‐secreting γδ T cells function as a part of mucosal defence against infection, with most studies to date focusing on their response to bacterial pathogens. γδ 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 RORγt 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.