Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages

LE Harrington, RD Hatton, PR Mangan, H Turner… - Nature …, 2005 - nature.com
LE Harrington, RD Hatton, PR Mangan, H Turner, TL Murphy, KM Murphy, CT Weaver
Nature immunology, 2005nature.com
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 …
Abstract
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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