The Role And Mechanism Of T Cells PPAR? In Chronic Rejection Of Murine Cardiac Transplantation

Background:Heart transplantation is more and more importantin the clinicaltreatment of end-stage heart disease nowadays, while Chronic allograftrejectionis still the key challenge for the long-termsurvival of whom received heart transplantoperation. The immunoregulatoryfunctions of PPAR Y hasbeen foundin T cellsandmacrophages. Despite of this, details in PPAR Y's effects on immune cells remains unknown during chronic allograft rejection because of the complexpathological process of chronic rejection,as well as the effectsofPPAR ? on multiple immune cells.Objective:Exploring the role and mechanism of PPAR?-deficient T Cells in chronic rejection of murine cardiac transplantation.Methods:We used bm12 mice as donors to establish chronic rejection model, andMHC-IImismatched T-cell-specific PPAR Y knockout mice or wild type (WT) littermates as recipients. Histology and immunohistochemistry were taken to detect the allograft pathology. We isolated T cells infiltrating in the allograft, and usedcytokine arrays and flow cytometry to detect cytokines andsubpopulations. RT-PCR was taken in measuring the transcription levels in the allograft. In vitro, the subpopulations of T cells were tested after culture in various polarizing conditions. To investigate their ability to induceAAM, PPAR ?-deficientTreg were cocultured with monocytes.Results:We see that T cell-specific PPAR? knockout recipients had reduced cardiac allograft survival and an increased degree ofpathology compared with WT littermates. There are more CD4+T cells infiltrating into the allograft T cell-specificPPAR? knockout and altered the Th1/Th2 and Th17/Treg ratios, meanwhile, PPAR? deficiency in Tcells reduced the polarization of A AM through the action of Th2 and Treg. The pioglitazone-induced polarization of reduced allograft survival was eliminated by PPAR?-deficient T cells.Conclusion:PPAR?-deficient T cells influenced the T cell subset and AAM polarization in chronic allograft rejection. We could yield a new treatment without side effects according tomechanism of PPAR? activation in transplantation tolerance.