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 |
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Pages (from-to) | 437-446 |
Number of pages | 10 |
Journal | Clinical Immunology |
Volume | 133 |
Issue number | 3 |
DOIs | |
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