Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment

Nat Immunol. 2009 Dec;10(12):1260-6. doi: 10.1038/ni.1821. Epub 2009 Nov 1.

Abstract

How naive CD4(+) T cells commit to the T helper type 2 (T(H)2) lineage is poorly understood. Here we show that the basic helix-loop-helix transcription factor Dec2 was selectively expressed in T(H)2 cells. CD4(+) T cells from Dec2-deficient mice showed defective T(H)2 differentiation in vitro and in vivo in an asthma model and in response to challenge with a parasite antigen. Dec2 promoted expression of interleukin 4 (IL-4), IL-5 and IL-13 during early T(H)2 differentiation and directly bound to and activated transcription of genes encoding the transcription factors JunB and GATA-3. As GATA-3 induces Dec2 expression, our findings also indicate a feed-forward regulatory circuit during T(H)2 differentiation.

Publication types

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

MeSH terms

  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Cell Differentiation
  • Cell Lineage*
  • Disease Models, Animal
  • GATA3 Transcription Factor / metabolism
  • Mice
  • Mice, Knockout
  • Protein Binding
  • Proto-Oncogene Proteins c-jun / metabolism
  • Th2 Cells / cytology*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Transcription Factors / deficiency
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism

Substances

  • Bhlhb3 protein, mouse
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Proto-Oncogene Proteins c-jun
  • Transcription Factors