RT Journal Article
SR Electronic
T1 Cutting Edge: Role of IL-27/WSX-1 Signaling for Induction of T-Bet Through Activation of STAT1 During Initial Th1 Commitment
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 4886
OP 4890
DO 10.4049/jimmunol.170.10.4886
VO 170
IS 10
A1 Takeda, Atsunobu
A1 Hamano, Shinjiro
A1 Yamanaka, Atsushi
A1 Hanada, Toshikatsu
A1 Ishibashi, Tatsuro
A1 Mak, Tak W.
A1 Yoshimura, Akihiko
A1 Yoshida, Hiroki
YR 2003
UL http://www.jimmunol.org/content/170/10/4886.abstract
AB 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.