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

A Takeda, S Hamano, A Yamanaka… - The Journal of …, 2003 - journals.aai.org
A Takeda, S Hamano, A Yamanaka, T Hanada, T Ishibashi, TW Mak, A Yoshimura
The Journal of Immunology, 2003journals.aai.org
WSX-1 is a member of the class I cytokine receptor family with homology to IL-12Rβ2 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-γ production by wild-type CD4+ T cells, IL-12-dependent IFN-γ …
Abstract
WSX-1 is a member of the class I cytokine receptor family with homology to IL-12Rβ2 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-γ production by wild-type CD4+ T cells, IL-12-dependent IFN-γ 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-12Rβ2 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.
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