First Author | Yang Y | Year | 2005 |
Journal | J Immunol | Volume | 174 |
Issue | 5 | Pages | 2720-9 |
PubMed ID | 15728480 | Mgi Jnum | J:97712 |
Mgi Id | MGI:3576164 | Doi | 10.4049/jimmunol.174.5.2720 |
Citation | Yang Y, et al. (2005) IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4 T cell activation. J Immunol 174(5):2720-9 |
abstractText | The transcription factor c-Maf plays a critical and selective role in IL-4 gene transcription. Little is known about the mechanism that guides c-Maf regulation during early T cell activation. We report that IL-6 but not IL-4 or other cytokines, rapidly up-regulates c-Maf transcription, as early as 3 h after TCR activation in naive CD4(+) T cells. c-Maf induction requires both IL-6- and TCR-initiated signals, and is independent of IL-4/Stat6 signals. Cyclosporin A and FK506, which target calcineurin and thereby inhibit TCR-mediated Ca(2+) signal pathways, block IL-6-mediated c-Maf expression. We show that Stat3 binds the c-maf promoter in CD4 T cells after IL-6 stimulation, and also transactivates the c-maf promoter in reporter gene assays. IL-6 induces similar c-Maf expression in protein kinase Ctheta-deficient CD4(+) T cells. Furthermore, IL-6 enhances IL-4 gene expression very early after TCR activation in both wild-type and Stat6-deficient CD4(+) T cells. Our findings suggest that IL-6 plays a unique role in initiating c-Maf expression after TCR engagement, and may subsequently regulate early IL-4 production and Th2 commitment. |