BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection

J Exp Med. 2017 May 1;214(5):1313-1331. doi: 10.1084/jem.20161076. Epub 2017 Mar 29.


Inappropriate IL-17 responses are implicated in chronic tissue inflammation. IL-23 contributes to Trypanosoma cruzi-specific IL-17 production, but the molecular mechanisms underlying regulation of the IL-23-IL-17 axis during T. cruzi infection are poorly understood. Here, we demonstrate a novel function of BATF2 as a negative regulator of Il23a in innate immune cells. IL-17, but not IFN-γ, was more highly produced by CD4+ T cells from spleens and livers of T. cruzi-infected Batf2-/- mice than by those of wild-type mice. In this context, Batf2-/- mice showed severe multiorgan pathology despite reduced parasite burden. T. cruzi-induced IL-23 production was increased in Batf2-/- innate immune cells. The T. cruzi-induced enhanced Th17 response was abrogated in Batf2-/-Il23a-/- mice. The interaction of BATF2 with c-JUN prevented c-JUN-ATF-2 complex formation, inhibiting Il23a expression. These results demonstrate that IFN-γ-inducible BATF2 in innate immune cells controls Th17-mediated immunopathology by suppressing IL-23 production during T. cruzi infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / physiology*
  • Chagas Disease / immunology*
  • Chagas Disease / pathology
  • Female
  • Immunity, Innate / immunology
  • Interleukin-23 Subunit p19 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-jun / physiology
  • Th17 Cells / immunology
  • Th17 Cells / physiology*
  • Trypanosoma cruzi / immunology*


  • BATF2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Il23a protein, mouse
  • Interleukin-23 Subunit p19
  • Proto-Oncogene Proteins c-jun