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

Academic Article

Abstract

  • 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 ofautoimmune 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 ofIFN-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 andRunx transcription factors in the generation of pathogenic IFN-γ-producing Th17 cells. © 2014 Elsevier Inc.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 8606559
  • Author List

  • Wang Y; Godec J; Ben-Aissa K; Cui K; Zhao K; Pucsek AB; Lee YK; Weaver CT; Yagi R; Lazarevic V
  • Start Page

  • 355
  • End Page

  • 366
  • Volume

  • 40
  • Issue

  • 3