Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells

Immunity. 1999 Dec;11(6):677-88. doi: 10.1016/s1074-7613(00)80142-9.

Abstract

Stat6 is critical for IL-4-mediated Th2 cell development, but its molecular mechanism remains unclear. Here we constructed Stat6:ER, a Stat6-estrogen receptor fusion protein that can be activated by 4-hydroxy-tamoxifen, independently of IL-4 and endogenous Stat6. Retrovirus-mediated introduction of Stat6:ER into developing Th1 cells induced Th2-specific cytokines and suppressed IFNgamma production in a 4-HT-dependent manner and in the absence of IL-4. It also induced GATA-3 and c-maf expression and downregulated IL-12Rbeta2 chain expression. Its decreased ability to induce the Th2 phenotype with progressing Th1 cell commitment correlated with a decreased induction of GATA-3 and c-maf. This study indicates that Stat6 functions upstream of GATA-3 and c-Maf to induce Th2 development.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Division
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • GATA3 Transcription Factor
  • Gene Expression Regulation
  • Genetic Vectors / genetics
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-12 / genetics
  • Interleukin-4 / immunology
  • Interleukin-4 / pharmacology
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-maf
  • Receptors, Estrogen / agonists
  • Receptors, Estrogen / genetics
  • Recombinant Fusion Proteins / genetics
  • Retroviridae / genetics
  • STAT6 Transcription Factor
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Time Factors
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcriptional Activation

Substances

  • Cytokines
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Maf protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-maf
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Tamoxifen
  • afimoxifene
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • DNA