Tim-1-Fc suppresses chronic cardiac allograft rejection and vasculopathy by reducing IL-17 production.

Tim-1-Fc suppresses chronic cardiac allograft rejection and vasculopathy by reducing IL-17 production. Int J Clin Exp Pathol. 2014;7(2):509-20 Authors: Shi X, Zhang M, Liu F, Wang Z, Zhang L, Cheng H, Zhang S, Fei T, Guo M, Bian J, Wang Q, Ding G Abstract Previously, we demonstrated that Tim-1-Fc prevents acute cardiac graft rejection by inhibiting Th1 response. In the present report, we tackled the impact of Tim-1-Fc on Th17 cells in a model of cardiac chronic rejection. Administration of Tim-1-Fc did not result in a detectable impact on innate immunity and regulatory T cells, while it provided protection for Bm12-derive cardiac grafts against chronic rejection in B6 recipients, as manifested by the reduction of inflammatory infiltration along with less severity of vasculopathy. Studies in T-bet(-/-) recipients by implanting Bm12-derived cardiac grafts further revealed that Tim-1-Fc significantly protected cardiac grafts from chronic rejection along with attenuated production of IL-17 producing T cells. Depletion of CD4 and CD8 T cells or blockade of IL-17 in T-bet(-/-) recipients demonstrated that Tim-1-Fc selectively suppresses Th17 differentiation along with attenuated IL-17 secretion. Together, our data suggest that Tim-1-Fc protects cardiac grafts from chronic rejection by suppressing CD4 Th17 development and functionality. Therefore, Tim-1-Fc might be a potential immunosuppressive agent in the setting of cardiac transplantation. ...
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research