Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice

被引：11

作者：

Fushimi, Soichiro ^{[1
]}

Ogino, Tetsuya ^{[1
]}

Hara, Junko ^{[1
]}

Takahata, Tomohiro ^{[1
]}

Wakabayashi, Hiroshi ^{[1
]}

Watanabe, Haruyuki ^{[1
]}

Arashima, Yasuharu ^{[1
]}

Kubo, Masato ^{[2
]}

Matsukawa, Akihiro ^{[1
]}

机构：

[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol & Expt Med, Okayama 7008558, Japan

[2] RIKEN, Yokohama Inst, Res Ctr Allergy & Immunol, Lab Signal Network, Yokohama, Kanagawa, Japan

来源：

CLINICAL IMMUNOLOGY | 2009年 / 133卷 / 03期

关键词：

Concanavalin A; Fas; Hepatotoxicity; NKT cells; SOCS; T cells; Th1; cytokine; Transcription factor; LIVER-INJURY; STAT3; SOCS3; INTERLEUKIN-22; INFLAMMATION; HEPATOCYTES; MACROPHAGES; MECHANISMS; CHEMOKINES; PLAYS;

D O I：

10.1016/j.clim.2009.08.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

T cells play central rotes in liver diseases, but the regulatory mechanism by cytokine signaling is not well understood. In the present study, we explored the role of SOCS3 in T cells in concanavalin A (ConA)-induced hepatitis. Mice with T-cell-specific overexpression of SOCS3 (SOCS3-cTg) showed reduced hepatic damage and improved mice survival relative to the control, an event that was associated with decreased apoptotic signals Fas and pStat1. Expression of Th1-cytokines/chemokines was decreased in SCCS3-cTg liver with reduced expression of T-bet, a Th1-transcription factor. Flow cytometric analysis of the liver lymphocytes demonstrated that activated CD4(+) T cells, cytotoxic T cells and. natural killer T cells were significantly decreased in SOCS3-cTg liver with decreased expression of perforin and granzyme 8, injurious molecules for hepatocyte damage. These results suggest that forced expression of SOCS3 in T cells prevents ConA-induced liver injury by inhibiting several phases of Th1 responses. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：437 / 446

页数：10

共 39 条

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