CD4+ T cells producing interleukin 17 (IL-17) are associated with autoimmunity, although the precise mechanisms that control their development are undefined. Here we present data that challenge the idea of a shared developmental pathway with T helper type 1 (TH1) or TH2 lineages and instead favor the idea of a distinct effector lineage we call 'TH-17'. The development of TH-17 cells from naive precursor cells was potently inhibited by interferon-γ (IFN-γ) and IL-4, whereas committed TH-17 cells were resistant to suppression by TH1 or TH2 cytokines. In the absence of IFN-γ and IL-4, IL-23 induced naive precursor cells to differentiate into TH-17 cells independently of the transcription factors STAT1, T-bet, STAT4 and STAT6. These findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
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We thank W. Ouyang and N. Ghilardi, and members of the Weaver laboratory for comments and suggestions. Supported by the National Institutes of Health (AI035783, AI057956 and DK64400 to C.T.W.), Sankyo (C.T.W.), Howard Hughes Medical Institute (K.M.M.) and the National Multiple Sclerosis Society (L.E.H.).
The authors declare no competing financial interests.
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Harrington, L., Hatton, R., Mangan, P. et al. Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6, 1123–1132 (2005). https://doi.org/10.1038/ni1254
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