Unlike ?? T cells, ?? T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22.

Apart from conventional CD4(+) Th17 cells, the cytokines IL-17A and IL-22 can also be produced by ?? T cells, NK cells and lymphoid tissue inducer (LTi) cells. Th17 cells develop from precursor cells after T-cell receptor stimulation in the presence of TGF-?, IL-6 and IL-23. In contrast, a subset of ?? T cells ("??T17") is committed for fast IL-17 production already in the thymus; however, ?? T cells can also produce IL-17 after prolonged in vitro stimulation via their ?? T-cell receptor plus IL-23. Here, we show that ?? T-, LTi- and NKT cells differ extensively from Th17 cells in their signalling requirements for the generation of IL-17A and IL-22. While production of these cytokines by Th17 cells totally depends on the transcription factor interferon regulatory factor 4 (IRF4), IRF4 is irrelevant in the other cell types. As for ?? T cells, this finding pertains to both thymic commitment and prolonged in vitro culture. Furthermore, IL-17A-producing ?? T cells accumulate in the central nervous system of IRF4 deficient (Irf4(-/-)) mice during experimental autoimmune encephalomyelitis. IL-17A-producing WT and Irf4(-/-) ?? T cells equally express CCR6 and lack CD27. The underlying IRF4-independent pathway partially involves STAT3 during in vitro stimulation.     «

Apart from conventional CD4(+) Th17 cells, the cytokines IL-17A and IL-22 can also be produced by ?? T cells, NK cells and lymphoid tissue inducer (LTi) cells. Th17 cells develop from precursor cells after T-cell receptor stimulation in the presence of TGF-?, IL-6 and IL-23. In contrast, a subset of ?? T cells ("??T17") is committed for fast IL-17 production already in the thymus; however, ?? T cells can also produce IL-17 after prolonged in vitro stimulation via their ?? T-cell receptor plus I...     »