論文 - 詳細
| RRC ID | 49632 |
|---|---|
| 著者 | Kitada S, Kayama H, Okuzaki D, Koga R, Kobayashi M, Arima Y, Kumanogoh A, Murakami M, Ikawa M, Takeda K. |
| タイトル | BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection. |
| ジャーナル | 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. |
| 巻・号 | 214(5) |
| ページ | 1313-1331 |
| 公開日 | 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 |
| 引用数 | 17 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 11 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pGAL3-IL23 promoter (RDB15467) pcDNA3.1(+)_Flag-BATF2 (RDB15468). |