Stat6 and c-Jun mediate Th2 cell-specific IL-24 gene expression

• Published in: The Journal of immunology (1950) 2011-04, Vol.186 (7), p.4098-4109
• Main Authors: Sahoo, Anupama, Lee, Choong-Gu, Jash, Arijita, Son, Jun-Seock, Kim, Gicheon, Kwon, Ho-Keun, So, Jae-Seon, Im, Sin-Hyeog
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Cell Line, Tumor; Epitopes, T-Lymphocyte - immunology; Gene Expression Regulation - immunology; HEK293 Cells; Humans; Interleukins - biosynthesis; Interleukins - genetics; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Promoter Regions, Genetic - immunology; Protein Binding - genetics; Protein Binding - immunology; Proto-Oncogene Proteins c-jun - physiology; Rats; Receptors, Antigen, T-Cell - physiology; STAT6 Transcription Factor - physiology; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism; Transcription Factor AP-1 - physiology; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1002620

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/+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.