| First Author | Kitada S | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 5 | Pages | 1313-1331 |
| PubMed ID | 28356392 | Mgi Jnum | J:242021 |
| Mgi Id | MGI:5904211 | Doi | 10.1084/jem.20161076 |
| Citation | Kitada S, et al. (2017) BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection. J Exp Med 214(5):1313-1331 |
| abstractText | 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-gamma, 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-gamma-inducible BATF2 in innate immune cells controls Th17-mediated immunopathology by suppressing IL-23 production during T. cruzi infection. |
