PT  - JOURNAL ARTICLE
AU  - Takeda, Atsunobu
AU  - Hamano, Shinjiro
AU  - Yamanaka, Atsushi
AU  - Hanada, Toshikatsu
AU  - Ishibashi, Tatsuro
AU  - Mak, Tak W.
AU  - Yoshimura, Akihiko
AU  - Yoshida, Hiroki
TI  - Cutting Edge: Role of IL-27/WSX-1 Signaling for Induction of T-Bet Through Activation of STAT1 During Initial Th1 Commitment
AID  - 10.4049/jimmunol.170.10.4886
DP  - 2003 May 15
TA  - The Journal of Immunology
PG  - 4886--4890
VI  - 170
IP  - 10
4099  - http://www.jimmunol.org/content/170/10/4886.short
4100  - http://www.jimmunol.org/content/170/10/4886.full
SO  - J. Immunol.2003 May 15; 170
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.