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.