RRC ID 54356
Author 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.
Title The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells.
Journal 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.
Volume 16(10)
Pages 1077-84
Published 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
Times Cited 40
DNA material pGL4-IL-9 promoter reporter (positions -464 to +284) (RDB16735)