Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment.
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.
Mesh Terms:
Animals, Cell Line, Cells, Cultured, DNA-Binding Proteins, Humans, Interferon-gamma, Interleukin-12, Interleukins, Janus Kinase 1, Mice, Mice, Knockout, Protein-Tyrosine Kinases, Receptors, Cytokine, Receptors, Interleukin, STAT1 Transcription Factor, Signal Transduction, T-Box Domain Proteins, Th1 Cells, Trans-Activators, Transcription Factors, Transcriptional Activation
Animals, Cell Line, Cells, Cultured, DNA-Binding Proteins, Humans, Interferon-gamma, Interleukin-12, Interleukins, Janus Kinase 1, Mice, Mice, Knockout, Protein-Tyrosine Kinases, Receptors, Cytokine, Receptors, Interleukin, STAT1 Transcription Factor, Signal Transduction, T-Box Domain Proteins, Th1 Cells, Trans-Activators, Transcription Factors, Transcriptional Activation
J. Immunol.
Date: May. 15, 2003
PubMed ID: 12734330
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