Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment

Immunity. 2000 Jan;12(1):27-37. doi: 10.1016/s1074-7613(00)80156-9.


The initial source of IL-4-inducing Th2 development and the mechanism of stable Th2 commitment remain obscure. We found the reduced level of IL-4 production in Stat6-deficient T cells to be significantly higher than in Th1 controls. Using a novel cell surface affinity matrix technique, we found that IL-4-secreting Stat6-deficient T cells stably expressed GATA-3 and Th2 phenotype. Introducing GATA-3 into Stat6-deficient T cells completely restored Th2 development, inducing c-Maf, Th2-specific DNase I hypersensitive sites in the IL-4 locus, and Th2 cytokine expression. The fact that GATA-3 fully reconstitutes Th2 development in Stat6-deficient T cells indicates it is a master switch in Th2 development. Finally, GATA-3 exerts Stat6-independent autoactivation, creating a feedback pathway stabilizing Th2 commitment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatin / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • GATA3 Transcription Factor
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / metabolism*
  • Mice
  • Mice, Transgenic
  • STAT6 Transcription Factor
  • Th1 Cells / metabolism
  • Th2 Cells / cytology*
  • Th2 Cells / metabolism
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Trans-Activators / physiology*
  • Transcriptional Activation*


  • Chromatin
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Interleukin-4