BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection.
BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection.
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DOI：
10.1084/jem.20161076
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发表时间：
2017-05-01
期刊：
影响因子：
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通讯作者：
Takeda K
中科院分区：
文献类型：
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作者：
Kitada S;Kayama H;Okuzaki D;Koga R;Kobayashi M;Arima Y;Kumanogoh A;Murakami M;Ikawa M;Takeda K
Kitada等证明，巨噬细胞和树突状细胞中IFN-γ诱导的转录因子BATF 2通过抑制T细胞增殖过程中IL-23的产生来预防Th 17介导的多器官病理学。克氏感染不适当的IL-17应答与慢性组织炎症有关。IL-23促进克氏锥虫特异性IL-17的产生，但T.对克氏病毒感染知之甚少。在这里，我们证明了BATF 2作为先天免疫细胞中IL 23 a的负调节剂的新功能。T淋巴细胞脾、肝CD 4 + T细胞产生IL-17的能力较强，而IFN-γ的产生能力较弱。Cruzi感染的Batf 2 −/−小鼠比野生型小鼠更明显。在这种情况下，Batf 2 −/−小鼠显示出严重的多器官病理学，尽管寄生虫负担减少。T. Cruzi诱导的Batf 2 −/−先天免疫细胞中IL-23的产生增加。霸王Cruzi诱导的增强的Th 17应答在Batf 2 −/− Il 23 a −/−小鼠中被消除。BATF 2与c-JUN的相互作用阻止了c-JUN-ATF-2复合物的形成，抑制了Il 23 a的表达。这些结果表明，IFN-γ诱导的BATF 2在先天性免疫细胞中通过抑制T.克氏感染
Kitada et al. demonstrate that transcription factor BATF2 induced by IFN-γ in macrophages and dendritic cells prevents Th17-mediated multiorgan pathology through suppression of IL-23 production during T. cruzi infection. 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.