The AP-1 transcription factor Batf controls T H 17 differentiation

Academic Article

Abstract

  • Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of JUN, FOS, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains. Many AP-1 proteins contain defined transcriptional activation domains, but BATF and the closely related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are considered to be inhibitors of AP-1 activity. Here we show that Batf is required for the differentiation of IL17-producing T helper (T H 17) cells. T H 17 cells comprise a CD4 + T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity. Batf-/- mice have normal T H 1 and T H 2 differentiation, but show a defect in T H 17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. Batf-/- T cells fail to induce known factors required for T H 17 differentiation, such as RORγt (encoded by Rorc) and the cytokine IL21 (refs 14-17). Neither the addition of IL21 nor the overexpression of RORγt fully restores IL17 production in Batf-/- T cells. The Il17 promoter is BATF-responsive, and after T H 17 differentiation, BATF binds conserved intergenic elements in the Il17a-Il17f locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in T H 17 differentiation. © 2009 Macmillan Publishers Limited. All rights reserved.
  • Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Schraml BU; Hildner K; Ise W; Lee WL; Smith WAE; Solomon B; Sahota G; Sim J; Mukasa R; Cemerski S
  • Start Page

  • 405
  • End Page

  • 409
  • Volume

  • 460
  • Issue

  • 7253