Other
16 Authors
- Chen H,
- Chen W,
- Zhang D,
- Chen Q,
- Deng L,
- Goldberg N,
- Zanvit P,
- Cui K,
- Maruyama T,
- Ishikawa M,
- Zhao K,
- Abbatiello B,
- Nakatsukasa H,
- Jin W,
- Sun L,
- Tu E
| First Author | Nakatsukasa H | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 10 | Pages | 1077-84 |
| PubMed ID | 26322481 | Mgi Jnum | J:233651 |
| Mgi Id | MGI:5787751 | Doi | 10.1038/ni.3252 |
| Citation | Nakatsukasa H, et al. (2015) The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells. Nat Immunol 16(10):1077-84 |
| abstractText | The molecular mechanisms by which signaling via transforming growth factor-beta (TGF-beta) 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-beta1 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. |
