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The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferon-γ-producing T helper 17 cells.

Wang, Yan; Godec, Jernej; Ben-Aissa, Khadija; Cui, Kairong; Zhao, Keji; Pucsek, Alexandra B; Lee, Yun Kyung; Weaver, Casey T; Yagi, Ryoji; Lazarevic, Vanja.
Immunity; 40(3): 355-66, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24530058
T helper 17 (Th17) cells can give rise to interleukin-17A (IL-17A)- and interferon (IFN)-γ-double-producing cells that are implicated in development of autoimmune diseases. However, the molecular mechanisms that govern generation of IFN-γ-producing Th17 cells are unclear. We found that coexpression of the Th1 and Th17 cell master transcription factors, T-bet and retinoid-related orphan receptor gamma-t (RORγt), respectively, did not generate Th cells with robust IL-17 and IFN-γ expression. Instead, development of IFN-γ-producing Th17 cells required T-bet and Runx1 or Runx3. IL-12-stimulated Th17 cells upregulated Runx1, which bound to the Ifng locus in a T-bet-dependent manner. Reciprocally, T-bet or Runx1 deficiency or inhibition of Runx transcriptional activity impaired the development of IFN-γ-producing Th17 cells during experimental autoimmune encephalomyelitis, which correlated with substantially ameliorated disease course. Thus, our studies identify a critical role for T-bet and Runx transcription factors in the generation of pathogenic IFN-γ-producing Th17 cells.
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