RRC ID 49632
Author Kitada S, Kayama H, Okuzaki D, Koga R, Kobayashi M, Arima Y, Kumanogoh A, Murakami M, Ikawa M, Takeda K.
Title BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection.
Journal J. Exp. Med.
Abstract 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.
Volume 214(5)
Pages 1313-1331
Published 2017-5-1
DOI 10.1084/jem.20161076
PII jem.20161076
PMID 28356392
PMC PMC5413328
MeSH 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*
IF 10.892
Resource
DNA material pGAL3-IL23 promoter (RDB15467) pcDNA3.1(+)_Flag-BATF2 (RDB15468).