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 › peer-review

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 2009

Keywords

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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.clim.2009.08.015

Fingerprint Dive into the research topics of 'Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice'. Together they form a unique fingerprint.

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 journal › Article › peer-review

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.

@article{a6fcae276bd3499fa49dc7708d81d2a5,

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

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.",

keywords = "Concanavalin A;, Fas;, Hepatotoxicity;, NKT cells;, SOCS;, T cells;, Th1 cytokine;, Transcription factor",

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

note = "Funding Information: This work was supported in part by grants from The Ministry of Education, Science, Sports and Culture , and The Ministry of Health and Welfare, Japan ., Wesco Scientific Promotion Foundation.",

year = "2009",

month = dec,

doi = "10.1016/j.clim.2009.08.015",

language = "English",

volume = "133",

pages = "437--446",

journal = "Clinical Immunology",

issn = "1521-6616",

publisher = "Academic Press Inc.",

number = "3",

}

TY - JOUR

T1 - Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice

AU - Fushimi, Soichiro

AU - Ogino, Tetsuya

AU - Hara, Junko

AU - Takahata, Tomohiro

AU - Wakabayashi, Hiroshi

AU - Watanabe, Haruyuki

AU - Arashima, Yasuharu

AU - Kubo, Masato

AU - Matsukawa, Akihiro

N1 - Funding Information: This work was supported in part by grants from The Ministry of Education, Science, Sports and Culture , and The Ministry of Health and Welfare, Japan ., Wesco Scientific Promotion Foundation.

PY - 2009/12

Y1 - 2009/12

N2 - 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.

AB - 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.

KW - Concanavalin A;

KW - Fas;

KW - Hepatotoxicity;

KW - NKT cells;

KW - SOCS;

KW - T cells;

KW - Th1 cytokine;

KW - Transcription factor

UR - http://www.scopus.com/inward/record.url?scp=70350605493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350605493&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2009.08.015

DO - 10.1016/j.clim.2009.08.015

M3 - Article

C2 - 19766538

AN - SCOPUS:70350605493

VL - 133

SP - 437

EP - 446

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this