SOCS3 in T and NKT cells negatively regulates cytokine production and ameliorates ConA-induced hepatitis

Mako Nakaya, Masayuki Hashimoto, Ryusuke Nakagawa, Yu Wakabayashi, Takuma Ishizaki, Ichiro Takada, Kyoko Komai, Hiroki Yoshida, Akihiko Yoshimura

研究成果: Article査読

35 被引用数 (Scopus)

抄録

Suppressor of cytokine signaling 3 (SOCS3), a negative-feedback molecule for cytokine signaling, has been implicated in protection against liver injury. Previous studies have shown that overexpression of SOCS3 in the liver by adenovirus or membrane permeable recombinant protein protected the liver from various injuries. However it remained uncertain in which type of cells SOCS3 suppresses liver injury. In this study, we demonstrated that forced expression of SOCS3 in T and NKT cells suppressed ConA-induced hepatitis using T and NKT cell-specific SOCS3 transgenic (Lck-SOCS3 Tg) mice. IFN-γ and IL-4 production was reduced in Lck-SOCS3 Tg mice as well as splenocytes treated with ConA. IFN-γ and IL-4 levels were also reduced in Lck-SOCS3 Tg mice administrated with α-galactosylceramide, suggesting that SOCS3 in NKT cells has suppressive function. Sustained expression of SOCS3 in an NKT cell line also resulted in reduced expression of various cytokines and transcription factors. In contrast, T and NKT cell-specific SOCS3 conditional knockout (Lck-SOCS3 cKO) mice were hypersensitive to ConA-mediated hepatitis. Isolated SOCS3-deficient NKT cells produced higher levels of IFN-γ and IL-4. These data indicate that SOCS3 plays a negative regulatory role in NKT cell activation and that forced expression of SOCS3 in NKT cells is effective in preventing hepatitis.

本文言語English
ページ(範囲)7047-7053
ページ数7
ジャーナルJournal of Immunology
183
11
DOI
出版ステータスPublished - 2009 12 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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