The Effects And Mechanisms Underlying SOCS3 Gene Transfer Prolongs The Survival Of Murine Cardiac Allograft

Objective: To investigate the regulatory effect and underlying mechanisms of SOCS3 (Suppressor of cytokine signaling 3) on the survival time and inflammatory cell infiltration of cardiac allograft, and on the differentiation of T lymphocyte of splenocyte after cardiac transplantation.Methods: The murine cardiac transplantation model was established (from BALB/C(H-2d to C57BL/6J(H-2b)), in which the mice were randomly assigned into three groups: SOCS3 group, PBS group, and empty vector group. The donors and recipients of each group were received tail intravenous injection with 100μg plasmid pEF-FLAG-I/mSOCS3 in 300μl PBS, 300μl PBS, and 100μg empty plasmid in 300μl PBS respectively for 3 days before operation, and the recipients continued to be injected for another 3 days after operation. 4 mice in each group were observed until death to compare the survival time of cardiac allograft. The hearts of another 4 mice in each group were collected and examined by HE staining for cardiac pathohistology, and by immunohistochemistry for the expression of CD3, F4/80, Gr1, SOCS3, STAT3 and pSTAT3, and the spleens were obtained to measure the differentiation of T cells via flow cytometry at different time point after transplantation.Results: Compared with PBS group and empty vector group, effective expression of SOCS3 in SOCS3 group treated with plasmid pEF-FLAG-I/mSOCS3 can prolong the survival time of cardiac allograft (P <0.05), reduce the infiltration of T lymphocyte and macrophage and the expression of STAT3 and pSTAT3 in cardiac grafts on 4th postoperative day, and decrease the amounts of CD4+IL-17+ cells and CD8+IL-17+ cells of spleens (P <0.05) on the second and fourth postoperative day. However, there were no significant differences of CD4+ IFNγ+ cells and CD8+ IFNγ+ cells among the three groups (P >0.05).Conclusion: SOCS3 gene transfer can inhibit the phosphorylation of STAT3, and then block the STAT3 signalling pathway, which maybe suppress the differentiation of IL-17+T cells, the infiltrations of T lymphocytes and macrophages, and result in the prolongation of the survival time of cardiac allograft eventually, but the concrete mechanisms need further investigation.