Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene

Immunity. 2001 Aug;15(2):275-87. doi: 10.1016/s1074-7613(01)00182-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • DNA Methylation
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • GATA3 Transcription Factor
  • Interleukin-4 / genetics
  • Mice
  • Mice, Mutant Strains
  • Polycomb Repressive Complex 1
  • Polycomb-Group Proteins
  • Repressor Proteins / genetics*
  • Th2 Cells / cytology*
  • Th2 Cells / immunology*
  • Trans-Activators / biosynthesis


  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Pcgf6 protein, mouse
  • Polycomb-Group Proteins
  • Repressor Proteins
  • Trans-Activators
  • Interleukin-4
  • Polycomb Repressive Complex 1