Journal
NATURE IMMUNOLOGY
Volume 16, Issue 10, Pages 1077-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3252
Keywords
-
Categories
Funding
- 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
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available