Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation

Immunity. 2002 May;16(5):733-44. doi: 10.1016/s1074-7613(02)00317-5.

Abstract

IL-4 is important in Th2 differentiation and in cell expansion. Stat6 is necessary and sufficient for both functions. Although Gata3 is critical for Th2 polarization, it is not sufficient to mediate IL-4-driven cell expansion. We report that growth factor independent-1 (Gfi-1), a Stat6-dependent transcriptional repressor, strikingly increases Th2 cell expansion by promoting proliferation and preventing apoptosis. Cells infected with a Gfi-1 retrovirus show striking enhancement of IL-2-induced Stat5 phosphorylation and repression of p27(Kip-1) expression, suggesting a potential mechanism for the Gfi-1 growth effect. The synergy of Gfi-1 and Gata3 provides a mechanism through which IL-4 could selectively promote Th2 cell expansion.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Apoptosis
  • Cells, Cultured
  • Coculture Techniques
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • GATA3 Transcription Factor
  • Genetic Vectors
  • Interleukin-4 / pharmacology*
  • Kinetics
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Models, Immunological
  • RNA, Messenger / biosynthesis
  • Retroviridae / genetics
  • STAT6 Transcription Factor
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology
  • Transcription Factors*

Substances

  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Gfi1 protein, mouse
  • RNA, Messenger
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Interleukin-4