The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Nature immunology - 16(2015), 10 vom: 01. Okt., Seite 1077-84 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nakatsukasa, Hiroko [VerfasserIn] |
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| Links: |
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| Themen: |
147785-34-0 |
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| Anmerkungen: |
Date Completed 19.01.2016 Date Revised 08.10.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/ni.3252 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM252307674 |
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| 245 | 1 | 4 | |a The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Zhang, Dunfang |e verfasserin |4 aut | |
| 700 | 1 | |a Maruyama, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Kairong |e verfasserin |4 aut | |
| 700 | 1 | |a Ishikawa, Masaki |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Zanvit, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Tu, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Wenwen |e verfasserin |4 aut | |
| 700 | 1 | |a Abbatiello, Brittany |e verfasserin |4 aut | |
| 700 | 1 | |a Goldberg, Nathan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qianming |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lingyun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Keji |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, WanJun |e verfasserin |4 aut | |
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