The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells

Nat Immunol. 2008 Jan;9(1):34-41. doi: 10.1038/ni1538. Epub 2007 Dec 2.


Interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) drive T helper type 1 (T(H)1) differentiation, but the mechanisms underlying the regulation of the complicated gene networks involved in this differentiation are not fully understood. Here we show that the IFN-gamma-induced transcription factor IRF1 was essential in T(H)1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor beta1 subunit (IL-12Rbeta1). IRF1 directly interacted with and activated the Il12rb1 promoter in CD4+ T cells. Notably, the IRF1-dependent induction of IL-12Rbeta1 was essential for IFN-gamma-IL-12 signaling but was dispensable for IL-23-IL-17 signaling. Because both IL-12 and IL-23 bind to and transmit signals through IL-12Rbeta1, our data suggest that distinct thresholds of IL-12Rbeta1 expression are required for T(H)1 versus T(H)-17 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / physiology*
  • Interferon-gamma / immunology*
  • Interleukin-12 / physiology*
  • Interleukin-17 / physiology
  • Interleukin-23 / physiology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Receptors, Interleukin-12 / physiology
  • Signal Transduction
  • Th1 Cells / cytology
  • Th1 Cells / immunology*


  • Il12rb1 protein, mouse
  • Interferon Regulatory Factor-1
  • Interleukin-17
  • Interleukin-23
  • Irf1 protein, mouse
  • Receptors, Interleukin-12
  • Interleukin-12
  • Interferon-gamma