期刊
NATURE IMMUNOLOGY
卷 16, 期 10, 页码 1077-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3252
关键词
-
类别
资金
- National Institute of Dental and Craniofacial Research (US National Institutes of Health)
- JSPS Research Fellowship Program for Japanese Biomedical and Behavioral Researchers at the US National Institutes of Health
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 (T(H)9 cells) remain incompletely understood. We found here that the DNA-binding inhibitor Id3 regulated T(H)9 differentiation, as deletion of Id3 increased IL-9 production from CD4(+) T cells. Mechanistically, TGF-beta 1 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 T(H)9 differentiation regulated anti-tumor immunity in an experimental melanomabearing 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 T(H)9 differentiation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据