Administration Of Interleukin-35 Inhibits Acute Rejection Of Cardiac Allograft In Mice

ObjectiveAs a new research of immunosuppression,IL-35 has been studied in autoimmune diseases and tumor-related diseases,while few studies on transplant rejection.This study is mainly to explore whether IL-35 can effectively inhibit acute rejection in heterotopic cardiac transplantation models,to explore the possible mechanism of IL-35 in inhibiting acute rejection of graft heart,to further study the mechanism of IL-35 in inhibiting acute graft rejection,and to study the effect of IL-35 on chronic rejection.Methods1.The heterotopic cardiac transplantation models was performed from Balb/c(25±3g)toC57 mice(25±3g).2.To compare the survival rate of IL-35 group,saline group and blank control group,and to observe whether IL-35 can effectively inhibit the acute rejection of transplanted heart.3.By staining the transplanted heart with HE staining,Immunohistochemistry,and Flow Staining of the transplanted heart and recipient spleen,we investigated the possibility mechanism of IL-35 inhibiting acute cardiac allograft rejection in a mouse cardiac allograft model.Results1.IL-35 significantly prolonged the survival time of transplanted heart in mice.The average survival time of experimental group(n=8)was 16.13(+1.44)days,that of saline group(n=8)was 8.63(+0.97)days,and that of blank control group(n=8)was 8.75(+1.25)days.2.HE staining,Immunohistochemistry,and Flow Staining analysis showed that IL-35 can significantly reduce the infiltration of CD4+,CD8+ T cells and CD19+ B cells in the myocardium of mice,and protect the normal structure of the graft heart.Maintaining the normal function of the heart significantly inhibits the acute rejection of the transplanted heart.At the same time,IL-35 significantly reduced the expression of CD8+ T cells and CD3-NK1.1+ NK cells in the spleen of the recipient,and the expression of CD4+CD25+FOXP3+Treg cells and IL-35+ B lymphocytes were significantly increased.ConclusionIL-35 can significantly prolong the survival time of transplanted hearts in mice,and can significantly reduce the infiltration of myocardial lymphocytes in the transplanted heart of mice,protect the normal structure of the heart of the graft,maintain the normal function of the heart,and significantly inhibit the acute rejection in heart transplantation.