Stat6 and c-Jun Mediate Th2 Cell-Specific IL-24 Expression Anupama Sahoo, Choong-Gu Lee, Arijita Jash, Jun-Seock Son, Gicheon Kim, Ho-Keun Kwon, Jae-Seon So and This information is current as Sin-Hyeog Im of September 28, 2021. J Immunol 2011; 186:4098-4109; Prepublished online 25 February 2011; doi: 10.4049/jimmunol.1002620

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Stat6 and c-Jun Mediate Th2 Cell-Specific IL-24

Anupama Sahoo, Choong-Gu Lee, Arijita Jash, Jun-Seock Son, Gicheon Kim, Ho-Keun Kwon, Jae-Seon So, and Sin-Hyeog Im

TCR signaling regulates multiple aspects of T cell function by controlling expression of various . IL-24 is a mul- tifunctional cytokine belonging to the IL-10 family. It displays anticancer effects in diverse cells and regulates immuno- pathology of and rheumatoid . IL-24 also plays an important role in 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 (2157/+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 Downloaded from AP-1 (c-Jun) to the IL-24 promoter locus in Th2 cells synergistically transactivated the IL-24 promoter. Stat6 and c-Jun 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. The Journal of Immunology, 2011, 186: 4098–4109. http://www.jimmunol.org/

roper differentiation of naive precursor T cells into effector role of chromatin remodeling and opposing epigenetic regulation T cells is necessary to regulate diverse immune responses mechanisms for transcription of cytokine genes in mammalian P through coordinated expression of lineage-specific cyto- cells, including genes that encode IL-4 and IFN-g (6–9). kine genes (1, 2). Mutually exclusive patterns of cyto