Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment

J Immunol. 2003 May 15;170(10):4886-90. doi: 10.4049/jimmunol.170.10.4886.

Abstract

WSX-1 is a member of the class I cytokine receptor family with homology to IL-12R beta 2 and is essential for the initial mounting of Th1 responses. STAT1 interacts with tyrosine-phosphorylated WSX-1, and the conserved tyrosine residue of the cytoplasmic domain of WSX-1 is essential for transcriptional activation of STAT1. IL-27 stimulation induced STAT1 phosphorylation in wild-type but not in WSX-1-deficient naive CD4(+) T cells. Although IL-27 did not directly induce IFN-gamma production by wild-type CD4(+) T cells, IL-12-dependent IFN-gamma production was augmented by IL-27 stimulation in wild-type naive CD4(+) T cells but was impaired in WSX-1-deficient naive CD4(+) T cells. Additionally, IL-27 stimulation induced T-bet and IL-12R beta 2 expression in wild-type, but not in WSX-1-deficient, CD4(+) T cells. Thus, during the initiation of Th1 differentiation, the IL-27/WSX-1 signaling system plays a pivotal role by STAT1-mediated T-bet induction before the IL-12R system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interleukin-12 / pharmacology
  • Interleukins / physiology*
  • Janus Kinase 1
  • Mice
  • Mice, Knockout
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Receptors, Cytokine / physiology*
  • Receptors, Interleukin
  • STAT1 Transcription Factor
  • Signal Transduction / immunology*
  • T-Box Domain Proteins
  • Th1 Cells / enzymology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism*
  • Trans-Activators / metabolism*
  • Transcription Factors / biosynthesis*
  • Transcriptional Activation / immunology*

Substances

  • DNA-Binding Proteins
  • IL27RA protein, human
  • Il27 protein, mouse
  • Il27ra protein, mouse
  • Interleukins
  • MYDGF protein, human
  • Receptors, Cytokine
  • Receptors, Interleukin
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Stat1 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Trans-Activators
  • Transcription Factors
  • Interleukin-12
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1