WSX-1 over-expression in CD4+ T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation

Atsunobu Takeda, Shinjiro Hamano, Hiroshi Shiraishi, Takeru Yoshimura, Hisanobu Ogata, Kazunari Ishii, Tatsuro Ishibashi, Akihiko Yoshimura, Hiroki Yoshida

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

WSX-1 is a component of the IL-27R. Analyses of WSX-1 knockout (WSX-1-/-) mice have shown that IL-27/WSX-1 signaling is essential for the proper development of Th1 responses and that WSX-1 can suppress cellular activation and pro-inflammatory cytokine production. We have generated transgenic mouse lines over-expressing the WSX-1 gene under the control of the T cell-specific CD2 promoter (WSX-1 Tg mice). Unexpectedly, like activated CD4+ T cells from WSX-1-/- mice, activated CD4+ T cells from WSX-1 Tg mice showed increased proliferation, augmented IL-2 production and up-regulated surface expression of activation markers. IL-27-mediated tyrosine phosphorylation of STAT1 was also enhanced in WSX-1 Tg CD4+ T cells, but STAT3 activation was normal. Exogenous IL-27 supported the proliferation of wild-type CD4+ T cells but suppressed that of WSX-1 Tg cells. WSX-1 over-expression increased IFN-γ production in Th1-polarized CD4+ T cells, but also promoted Th2 cytokine production under Th 1-polarizing conditions. Importantly, WSX-1 over-expression failed to suppress Th2 cytokine production under Th 2-polarizing conditions. Cytokine hyperproduction was also observed in vivo in WSX-1 Tg mice injected with Con A. Our data suggest that WSX-1 plays a pivotal role in regulating T cell responsiveness to TCR stimulation and that the correct balance of STAT1/STAT3 activation downstream of IL-27R engagement is crucial for the physiological function of IL-27.

Original languageEnglish
Pages (from-to)889-897
Number of pages9
JournalInternational immunology
Volume17
Issue number7
DOIs
Publication statusPublished - 2005 Jul

Keywords

  • CD4
  • Cytokine
  • IL-27
  • Transgene

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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