Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice.
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.
Fushimi
Soichiro
S
Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Okayama 700-8558, Japan.
Ogino
Tetsuya
T
Hara
Junko
J
Takahata
Tomohiro
T
Wakabayashi
Hiroshi
H
Watanabe
Haruyuki
H
Arashima
Yasuharu
Y
Kubo
Masato
M
Matsukawa
Akihiro
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D020169:Caspases / Q000235:genetics / Q000276:immunology; D003208:Concanavalin A; D053938:DNA Fragmentation; D053804:Granzymes / Q000096:biosynthesis; D006520:Hepatitis, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin / Q000096:biosynthesis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*
C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D003208:Concanavalin A; D054353:Perforin; D012313:RNA; D053804:Granzymes; D020169:Caspases