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

Atsunobu Takeda, Shinjiro Hamano, Atsushi Yamanaka, Toshikatsu Hanada, Tatsuro Ishibashi, Tak W. Mak, Akihiko Yoshimura, Hiroki Yoshida

Research output: Contribution to journalArticle

406 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4886-4890
Number of pages5
JournalJournal of Immunology
Volume170
Issue number10
DOIs
Publication statusPublished - May 15 2003

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Interleukin-27
T-Lymphocytes
Tyrosine
Cytokine Receptors
Interleukin-12
Transcriptional Activation
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Cutting edge : Role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. / Takeda, Atsunobu; Hamano, Shinjiro; Yamanaka, Atsushi; Hanada, Toshikatsu; Ishibashi, Tatsuro; Mak, Tak W.; Yoshimura, Akihiko; Yoshida, Hiroki.

In: Journal of Immunology, Vol. 170, No. 10, 15.05.2003, p. 4886-4890.

Research output: Contribution to journalArticle

Takeda, Atsunobu ; Hamano, Shinjiro ; Yamanaka, Atsushi ; Hanada, Toshikatsu ; Ishibashi, Tatsuro ; Mak, Tak W. ; Yoshimura, Akihiko ; Yoshida, Hiroki. / Cutting edge : Role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. In: Journal of Immunology. 2003 ; Vol. 170, No. 10. pp. 4886-4890.
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