title: Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene.
abstract: Polycomb group (PcG) gene products regulate homeobox gene expression in Drosophila and vertebrates and also cell cycle progression of immature lymphocytes. In a gene-disrupted mouse for polycomb group gene mel-18, mature peripheral T cells exhibited normal anti-TCR-induced proliferation; however, the production of Th2 cytokines (IL-4, IL-5, and IL-13) was significantly reduced, whereas production of IFNgamma was modestly enhanced. Th2 cell differentiation was impaired, and the defect was associated with decreased levels in demethylation of the IL-4 gene. Significantly, reduced GATA3 induction was demonstrated. In vivo antigen-induced IgG1 production and Nippostrongylus brasiliensis-induced eosinophilia were significantly affected, reflecting the deficit in Th2 cell differentiation. Thus, the PcG gene products play a critical role in the control of Th2 cell differentiation and Th2-dependent immune responses.
authors.affiliation: Department of Medical Immunology and Department of Molecular Immunology, Chiba University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: Y
authors.initials: Y
authors.lastname: Koseki
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: C
authors.initials: C
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Katsumoto
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: H
authors.initials: H
authors.lastname: Koseki
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D050990:GATA3 Transcription Factor; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology*; D015534:Trans-Activators / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C066476:Pcgf6 protein, mouse; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D015847:Interleukin-4; D063150:Polycomb Repressive Complex 1