Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis

Atsushi Yamanaka, Shinjiro Hamano, Yoshiyuki Miyazaki, Kazunari Ishii, Atsunobu Takeda, Tak W. Mak, Kunisuke Himeno, Akihiko Yoshimura, Hiroki Yoshida

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75 Citations (Scopus)

Abstract

Administration of Con A induces liver injury that is considered to be an experimental model for human autoimmune or viral hepatitis, where immunopathology plays roles mediated by activated lymphocytes, especially NK1.1+ CD3+ NKT cells, and inflammatory cytokines, including IFN-γ and IL-4. In the present study we investigated the role of WSX-1, a component of IL-27R, in Con A-induced hepatitis by taking advantage of WSX-1 knockout mice. WSX-1-deficient mice were more susceptible to Con A treatment than wild-type mice, showing serum alanine aminotransferase elevation and massive necrosis in the liver. Although the development of NKT cells appeared normal in WSX-1 knockout mice, purified NKT cells from the knockout mice produced more IFN-γ and IL-4 than those from wild-type mice in response to stimulation with Con A both in vitro and in vivo. In addition, hyperproduction of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, was observed in the knockout mice after Con A administration. These data revealed a novel role for WSX-1 as an inhibitory regulator of cytokine production and inflammation in Con A-induced hepatitis.

Original languageEnglish
Pages (from-to)3590-3596
Number of pages7
JournalJournal of Immunology
Volume172
Issue number6
DOIs
Publication statusPublished - 2004 Mar 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yamanaka, A., Hamano, S., Miyazaki, Y., Ishii, K., Takeda, A., Mak, T. W., Himeno, K., Yoshimura, A., & Yoshida, H. (2004). Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis. Journal of Immunology, 172(6), 3590-3596. https://doi.org/10.4049/jimmunol.172.6.3590