Dataset Information


The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells.

ABSTRACT: The molecular mechanisms by which signaling via transforming growth factor-? (TGF-?) 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-?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 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.

SUBMITTER: Nakatsukasa H 

PROVIDER: S-EPMC5935106 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

| GSE72051 | GEO
2019-01-01 | S-EPMC6612640 | BioStudies
2013-01-01 | S-EPMC3842015 | BioStudies
2017-01-01 | S-EPMC5961737 | BioStudies
2019-01-01 | S-EPMC6881360 | BioStudies
2011-01-01 | S-EPMC3140164 | BioStudies
2010-01-01 | S-EPMC3090036 | BioStudies
2017-01-01 | S-EPMC5606324 | BioStudies
| GSE86542 | GEO
1000-01-01 | S-EPMC5770389 | BioStudies