Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene.
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.
Kimura
M
M
Department of Medical Immunology and Department of Molecular Immunology, Chiba University, Japan.
Koseki
Y
Y
Yamashita
M
M
Watanabe
N
N
Shimizu
C
C
Katsumoto
T
T
Kitamura
T
T
Taniguchi
M
M
Koseki
H
H
Nakayama
T
T
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
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