IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells

J Interferon Cytokine Res. 2003 Sep;23(9):513-22. doi: 10.1089/10799900360708632.

Abstract

Interleukin-27 (IL-27) supports proliferation of naive CD4(+) T cells and enhances interferon-gamma (IFN-gamma) production by activated T cells and natural killer (NK) cells. We report here that IL-27 induces Stat1 and Stat3 phosphorylation and activation in human and murine cell lines and primary human T cells. IL-27 also induces T-Bet, a Stat1-dependent gene crucial to Th1 cell commitment. Similarly, IFN-alpha activates Stat1 and Stat3 and T-Bet expression in naive T cells. Induction of T-Bet results in upregulation of IL-12Rbeta2 on naive T cells, which is essential for responsiveness to IL-12 and differentiation to a Th1 phenotype. Both IL-27 and IFN-alpha induce expression of IL-12Rbeta2 in T cells. In contrast, IFN-gamma, which activates Stat1 but not Stat3, induces expression of T-Bet but not IL-12Rbeta2 in naive T cells. We propose that IL-27 and IFN-alpha are important for early Th1 commitment and act upstream of IL-12 and IFN-gamma in this pathway.

MeSH terms

  • DNA-Binding Proteins / metabolism
  • Humans
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism*
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Phosphorylation
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-12
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • T-Box Domain Proteins
  • T-Lymphocytes / metabolism*
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • IL27 protein, human
  • Interferon-alpha
  • Interleukins
  • MYDGF protein, human
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Trans-Activators
  • Transcription Factors