title: Stat6 and c-Jun mediate Th2 cell-specific IL-24 gene expression.
abstract: 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.
authors.affiliation: School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Anupama
authors.initials: A
authors.lastname: Sahoo
authors.forename: Choong-Gu
authors.initials: CG
authors.lastname: Lee
authors.forename: Arijita
authors.initials: A
authors.lastname: Jash
authors.forename: Jun-Seock
authors.initials: JS
authors.lastname: Son
authors.forename: Gicheon
authors.initials: G
authors.lastname: Kim
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Kwon
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: So
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D050800:STAT6 Transcription Factor / Q000502:physiology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000502:physiology; D014407:Tumor Cells, Cultured; D000099180:Interleukin-24
chemical_list: D018984:Epitopes, T-Lymphocyte; D007378:Interleukins; D016755:Proto-Oncogene Proteins c-jun; D011948:Receptors, Antigen, T-Cell; D050800:STAT6 Transcription Factor; D018808:Transcription Factor AP-1; D000099180:Interleukin-24; C494100:Stat6 protein, mouse