Dec2 promotes Th2 cell differentiation by enhancing IL-2R signaling

J Immunol. 2009 Nov 15;183(10):6320-9. doi: 10.4049/jimmunol.0900975. Epub 2009 Oct 30.

Abstract

Th cell differentiation is precisely regulated by thousands of genes at different stages. In the present study, we demonstrate that Dec2, a transcription factor belonging to the bHLH (basic helix-loop-helix) superfamily, is progressively induced during the course of Th2 differentiation, especially at the late stage. The up-regulated Dec2 can strongly promote Th2 development under Th2-inducing conditions, as evidenced by retrovirus-mediated gene transfer or transgenic manipulation. In addition, an enhancement of Th2 responses is also detectable in Dec2 transgenic mice in vivo. Conversely, RNA interference-mediated suppression of endogenous Dec2 could attenuate Th2 differentiation. Finally, we show that the enhanced Th2 development is at least in part due to substantial up-regulation of CD25 expression elicited by Dec2, thereby resulting in hyperresponsiveness to IL-2 stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / immunology
  • RNA, Small Interfering / immunology
  • RNA, Small Interfering / metabolism
  • Receptors, Interleukin-2 / immunology*
  • Receptors, Interleukin-2 / metabolism
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / immunology*
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • Transfection
  • Up-Regulation / immunology

Substances

  • Bhlhb3 protein, mouse
  • Cytokines
  • Interleukin-2
  • RNA, Small Interfering
  • Receptors, Interleukin-2
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Transcription Factors
  • Interleukin-4
  • Ovalbumin