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

Soichiro Fushimi, Tetsuya Ogino, Junko Hara, Tomohiro Takahata, Hiroshi Wakabayashi, Haruyuki Watanabe, Yasuharu Arashima, Masato Kubo, Akihiro Matsukawa

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

T cells play central roles 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 SOCS3-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 B, 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.

Original languageEnglish
Pages (from-to)437-446
Number of pages10
JournalClinical Immunology
Volume133
Issue number3
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Concanavalin A
Hepatitis
Cytokines
T-Lymphocytes
Liver
Natural Killer T-Cells
Chemokines
Liver Diseases
Hepatocytes
Transcription Factors
Lymphocytes
Wounds and Injuries

Keywords

  • Concanavalin A;
  • Fas;
  • Hepatotoxicity;
  • NKT cells;
  • SOCS;
  • T cells;
  • Th1 cytokine;
  • Transcription factor

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice. / Fushimi, Soichiro; Ogino, Tetsuya; Hara, Junko; Takahata, Tomohiro; Wakabayashi, Hiroshi; Watanabe, Haruyuki; Arashima, Yasuharu; Kubo, Masato; Matsukawa, Akihiro.

In: Clinical Immunology, Vol. 133, No. 3, 12.2009, p. 437-446.

Research output: Contribution to journalArticle

Fushimi, Soichiro ; Ogino, Tetsuya ; Hara, Junko ; Takahata, Tomohiro ; Wakabayashi, Hiroshi ; Watanabe, Haruyuki ; Arashima, Yasuharu ; Kubo, Masato ; Matsukawa, Akihiro. / Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice. In: Clinical Immunology. 2009 ; Vol. 133, No. 3. pp. 437-446.
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