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Stat6 and c-Jun mediate Th2 cell-specific IL-24 gene expression Sahoo A; Lee CG; Jash A; Son JS; Kim G; Kwon HK; So JS; Im SHJ Immunol 2011[Apr]; 186 (7): 4098-109TCR 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/+95 bp) 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.|Animals[MESH]|Base Sequence[MESH]|Cell Line, Tumor[MESH]|Epitopes, T-Lymphocyte/*immunology[MESH]|Gene Expression Regulation/*immunology[MESH]|HEK293 Cells[MESH]|Humans[MESH]|Interleukins/*biosynthesis/genetics[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Molecular Sequence Data[MESH]|Promoter Regions, Genetic/immunology[MESH]|Protein Binding/genetics/immunology[MESH]|Proto-Oncogene Proteins c-jun/*physiology[MESH]|Rats[MESH]|Receptors, Antigen, T-Cell/physiology[MESH]|STAT6 Transcription Factor/*physiology[MESH]|Th2 Cells/cytology/*immunology/*metabolism[MESH]|Transcription Factor AP-1/physiology[MESH]|Tumor Cells, Cultured[MESH] |
