[PDF][PDF] Late developmental plasticity in the T helper 17 lineage

YK Lee, H Turner, CL Maynard, JR Oliver, D Chen… - Immunity, 2009 - cell.com
YK Lee, H Turner, CL Maynard, JR Oliver, D Chen, CO Elson, CT Weaver
Immunity, 2009cell.com
Development of T helper (Th) 17 cells requires transforming growth factor (TGF)-β and
interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce
interferon (IFN)-γ are a recognized feature of Th17 cell responses, mice deficient for STAT4
and T-bet—two prototypical Th1 transcription factors—are protected from autoimmunity
associated with Th17 pathogenesis. To examine the fate and pathogenic potential of Th17
cells and origin of IFN-γ-producing T cells that emerge during Th17 immunity, we developed …
Summary
Development of T helper (Th) 17 cells requires transforming growth factor (TGF)-β and interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce interferon (IFN)-γ are a recognized feature of Th17 cell responses, mice deficient for STAT4 and T-bet—two prototypical Th1 transcription factors—are protected from autoimmunity associated with Th17 pathogenesis. To examine the fate and pathogenic potential of Th17 cells and origin of IFN-γ-producing T cells that emerge during Th17 immunity, we developed IL-17F reporter mice that identify cells committed to expression of IL-17F and IL-17A. Th17 cells required TGF-β for sustained expression of IL-17F and IL-17A. In the absence of TGF-β, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-γ production in a STAT4- and T-bet-dependent manner, albeit with distinct efficiencies. These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense.
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