| 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
|
| Times Cited |
17
|
| Resource |
| DNA material |
pGAL3-IL23 promoter (RDB15467)
pcDNA3.1(+)_Flag-BATF2 (RDB15468). |
