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Publication : IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4 T cell activation.

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.
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