c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-beta inhibits c-Maf-induced IL-21 production in CD4+ T cells.
J Leukoc Biol
; 87(4): 703-12, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-20042469
ABSTRACT
Previous studies have shown that IL-6 potently induces IL-21 production in CD4(+) T cells, whereas TGF-beta inhibits IL-6-induced IL-21 production in CD4(+) T cells. In this study, we addressed the mechanisms underlying the transcriptional regulation of IL-21 production in CD4(+) T cells. We found that IL-6 induced c-Maf expression in CD4(+) T cells and that the enforced expression of c-Maf induced IL-21 production in CD4(+) T cells without IL-6, IL-4/STAT6 signaling, or an autocrine effect of IL-21. Moreover, we found that c-Maf directly bound to and activated IL-21P and the CNS-2 enhancer through MARE sites. On the other hand, we also found that although TGF-beta up-regulated IL-6-induced c-Maf expression in CD4(+) T cells, TGF-beta inhibited c-Maf-induced IL-21 production in CD4(+) T cells. Finally, we found that Foxp3 bound to IL-21P and the CNS-2 enhancer and inhibited c-Maf-induced IL-21 production modestly but significantly in CD4(+) T cells. Taken together, these results suggest that c-Maf induces IL-21 production directly in CD4(+) T cells by activating IL-21P and the CNS-2 enhancer and that TGF-beta suppresses c-Maf-induced IL-21 production in CD4(+) T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Fator de Crescimento Transformador beta
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Elementos Facilitadores Genéticos
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Interleucinas
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Regiões Promotoras Genéticas
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Proteínas Proto-Oncogênicas c-maf
Limite:
Animals
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão