Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages

Nat Immunol. 2011 Jun;12(6):551-9. doi: 10.1038/ni.2030. Epub 2011 Apr 24.


Helper T cells control host defense against pathogens. The receptors for interleukin 12 (IL-12), IL-4 and IL-6 are required for differentiation into the T(H)1, T(H)2 and T(H)17 subsets of helper T cells, respectively. IL-2 signaling via the transcription factor STAT5 controls T(H)2 differentiation by regulating both the T(H)2 cytokine gene cluster and expression of Il4ra, the gene encoding the IL-4 receptor α-chain. Here we show that IL-2 regulated T(H)1 differentiation, inducing STAT5-dependent expression of the IL-12 receptor β2-chain (IL-12Rβ2) and the transcription factor T-bet, with impaired human T(H)1 differentiation when IL-2 was blocked. T(H)1 differentiation was also impaired in mouse Il2(-/-) T cells but was restored by IL-12Rβ2 expression. Consistent with the inhibition of T(H)17 differentiation by IL-2, treatment with IL-2 resulted in lower expression of the genes encoding the IL-6 receptor α-chain (Il6ra) and the IL-6 signal transducer gp130 (encoded by Il6st), and retroviral transduction of Il6st augmented T(H)17 differentiation even when IL-2 was present. Thus, IL-2 influences helper T cell differentiation by modulating the expression of cytokine receptors to help specify and maintain differentiated states.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Cytokine / genetics*
  • Receptors, Cytokine / metabolism
  • Receptors, Interleukin-12 / genetics
  • Receptors, Interleukin-12 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / metabolism


  • Interleukin-2
  • Receptors, Cytokine
  • Receptors, Interleukin-12
  • STAT5 Transcription Factor
  • Stat5a protein, mouse
  • Stat5b protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21

Associated data

  • GEO/GSE27158