Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression

Nat Immunol. 2008 Nov;9(11):1288-96. doi: 10.1038/ni.1656. Epub 2008 Sep 28.


T helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives T(H)2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor alpha-chain (IL-4Ralpha), was essential for inducing and maintaining IL-4Ralpha expression. Although IL-4 induced IL-4Ralpha expression, T cell receptor-induced IL-4Ralpha expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells. Notably, forced IL-4Ralpha expression restored the T(H)2 differentiation of Il2(-/-) cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with T(H)2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for T(H)2 differentiation and in maintaining the expression of Il4ra and other genes in T(H)2-committed cells.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Gene Expression Regulation*
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Interleukin-4 Receptor alpha Subunit / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • STAT5 Transcription Factor / metabolism
  • Th2 Cells / immunology*
  • Up-Regulation


  • Interleukin-2
  • Interleukin-4 Receptor alpha Subunit
  • STAT5 Transcription Factor

Associated data

  • GEO/GSE12346