論文 - 詳細
| RRC ID | 54356 |
|---|---|
| 著者 | Nakatsukasa H, Zhang D, Maruyama T, Chen H, Cui K, Ishikawa M, Deng L, Zanvit P, Tu E, Jin W, Abbatiello B, Goldberg N, Chen Q, Sun L, Zhao K, Chen W. |
| タイトル | The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells. |
| ジャーナル | Nat Immunol |
| Abstract |
The molecular mechanisms by which signaling via transforming growth factor-β (TGF-β) and interleukin 4 (IL-4) control the differentiation of CD4(+) IL-9-producing helper T cells (TH9 cells) remain incompletely understood. We found here that the DNA-binding inhibitor Id3 regulated TH9 differentiation, as deletion of Id3 increased IL-9 production from CD4(+) T cells. Mechanistically, TGF-β1 and IL-4 downregulated Id3 expression, and this process required the kinase TAK1. A reduction in Id3 expression enhanced binding of the transcription factors E2A and GATA-3 to the Il9 promoter region, which promoted Il9 transcription. Notably, Id3-mediated control of TH9 differentiation regulated anti-tumor immunity in an experimental melanoma-bearing model in vivo and also in human CD4(+) T cells in vitro. Thus, our study reveals a previously unrecognized TAK1-Id3-E2A-GATA-3 pathway that regulates TH9 differentiation. |
| 巻・号 | 16(10) |
| ページ | 1077-84 |
| 公開日 | 2015-10-1 |
| DOI | 10.1038/ni.3252 |
| PII | ni.3252 |
| PMID | 26322481 |
| PMC | PMC5935106 |
| MeSH | Animals CD4-Positive T-Lymphocytes / immunology* Cell Differentiation Cells, Cultured Flow Cytometry Humans Inhibitor of Differentiation Proteins / genetics Inhibitor of Differentiation Proteins / immunology* Interleukin-9 / biosynthesis* Interleukin-9 / immunology Mice Neoplasm Proteins / genetics Neoplasm Proteins / immunology* Polymerase Chain Reaction Signal Transduction / immunology |
| IF | 20.479 |
| 引用数 | 40 |
| 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 | News |
| 各媒体での言及数の合計 | 2 |
| 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 | pGL4-IL-9 promoter reporter (positions -464 to +284) (RDB16735) |