| First Author | Sahoo A | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 7 | Pages | 4098-109 |
| PubMed ID | 21357535 | Mgi Jnum | J:170694 |
| Mgi Id | MGI:4947156 | Doi | 10.4049/jimmunol.1002620 |
| Citation | Sahoo A, et al. (2011) Stat6 and c-Jun Mediate Th2 Cell-Specific IL-24 Gene Expression. J Immunol 186(7):4098-109 |
| abstractText | TCR signaling regulates multiple aspects of T cell function by controlling expression of various cytokine genes. IL-24 is a multifunctional cytokine belonging to the IL-10 family. It displays anticancer effects in diverse cancer cells and regulates immunopathology of psoriasis and rheumatoid arthritis. IL-24 also plays an important role in B cell differentiation. Mouse IL-24 gene is selectively expressed in activated Th2 cells upon TCR stimulation. However, the molecular mechanisms by which TCR stimulation induces IL-24 gene expression are still unclear. In this study, to elucidate the mechanism of Th2 cell-specific expression of IL-24, we identified a proximal promoter region (-157/+95bp) that plays critical role in activating the IL-24 gene in Th2 cells. This region has a Th2 cell-specific open chromatin structure along with permissive histone modifications. In vivo binding of Stat6 and AP-1 (c-Jun) to the IL-24 promoter locus in Th2 cells synergistically transactivated the IL-24 promoter. Stat6 and c-Jun proteins were found to physically cooperate with each other and upregulated IL-24 gene transcription. Knockdown of either Stat6 or c-Jun suppressed endogenous IL-24 gene expression in Th2 cells. In summary, TCR stimulation induces IL-24 expression in Th2 cells by the coordinate action of Stat6 and c-Jun transcription factors at the transcriptional level. |
