Notch directly regulates Gata3 expression during T helper 2 cell differentiation

Immunity. 2007 Jul;27(1):100-10. doi: 10.1016/j.immuni.2007.04.018. Epub 2007 Jul 19.

Abstract

Notch signaling plays multiple roles to direct diverse decisions regarding cell fate during T cell development. During helper T (Th) cell differentiation, Notch is involved in generating optimal Th2 cell responses. Here, we present data investigating how Notch mediates Th2 cell differentiation. Notch showed a CD4(+) T cell intrinsic role in promoting IL-4 expression that required GATA-3. In the absence of Notch signals, Gata3 expression was markedly diminished. Introduction of an activated allele of Notch1 into CD4(+) T cells led to the specific and direct upregulation of a developmentally regulated Gata3 transcript that included the exon 1a sequences. Furthermore, Notch acted in parallel with GATA-3 to synergistically activate IL-4 expression. Together, these data implicate Gata3 as a direct transcriptional Notch target that acts in concert with Notch signaling to generate optimal Th2 cell responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Down-Regulation / immunology
  • GATA3 Transcription Factor / antagonists & inhibitors
  • GATA3 Transcription Factor / biosynthesis
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Notch / physiology*
  • Signal Transduction / immunology
  • Th2 Cells / cytology*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism*

Substances

  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Receptors, Notch