Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling

Academic Article

Abstract

  • T helper (Th) 17 cells have been recently discovered in both mouse and human. Here we show that interleukin-1 (IL-1) signaling on T cells is critically required for the early programming of Th17 cell lineage and Th17 cell-mediated autoimmunity. IL-1 receptor1 expression in T cells, which was induced by IL-6, was necessary for the induction of experimental autoimmune encephalomyelitis and for early Th17 cell differentiation in vivo. Moreover, IL-1 signaling in T cells was required in dendritic cell-mediated Th17 cell differentiation from naive or regulatory precursors and IL-1 synergized with IL-6 and IL-23 to regulate Th17 cell differentiation and maintain cytokine expression in effector Th17 cells. Importantly, IL-1 regulated the expression of the transcription factors IRF4 and RORγt during Th17 cell differentiation; overexpression of these two factors resulted in IL-1-independent Th17 cell polarization. Our data thus indicate a critical role of IL-1 in Th17 cell differentiation and this pathway may serve as a unique target for Th17 cell-mediated immunopathology. © 2009 Elsevier Inc. All rights reserved.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 21235904
  • Author List

  • Chung Y; Chang SH; Martinez GJ; Yang XO; Nurieva R; Kang HS; Ma L; Watowich SS; Jetten AM; Tian Q
  • Start Page

  • 576
  • End Page

  • 587
  • Volume

  • 30
  • Issue

  • 4