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

doi:10.1016/j.clim.2009.08.015

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 journal › Article

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 language	English
Pages (from-to)	437-446
Number of pages	10
Journal	Clinical Immunology
Volume	133
Issue number	3
DOIs	https://doi.org/10.1016/j.clim.2009.08.015
Publication status	Published - Dec 1 2009

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Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Cite this

Fushimi, S., Ogino, T., Hara, J., Takahata, T., Wakabayashi, H., Watanabe, H., Arashima, Y., Kubo, M., & Matsukawa, A. (2009). Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice. Clinical Immunology, 133(3), 437-446. https://doi.org/10.1016/j.clim.2009.08.015

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, 01.12.2009, p. 437-446.

Research output: Contribution to journal › Article

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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Access to Document

10.1016/j.clim.2009.08.015