Effect of miR-744 on Ameliorating Heart Allograft Rejection in BALB/c Mice Via Regulation of TNFRSF4 Expression in Regulatory T Cells.

CD134 (TNFRSF4) is a member of the TNFR superfamily, which is specifically expressed on T cells. Previous studies have shown that blocking of CD134L-CD134 interaction reduces the percentage of activated T cells and prevents effector T cell–mediated graft rejection in heart transplantation. However, the role of microRNA-regulated inhibition of the CD134 signal in cardiac transplantation of T-regulatory (Treg) cells is not clear. In this study, we found microRNA 744 (miR-744) agomir administration enhanced the expression levels of miR-744 in CD4+CD25+ Treg cells from heart transplantation mice. Moreover, miR-744 agomir administration significantly enhanced the expression levels of CD62L and Ki67 in CD4+CD25+ Treg cells from heart transplantation mice and further enhanced immunosuppressive function of Treg cells following coculture with CD4+CD25- T cells for different ratios. In addition, miR-744 agomir treatment significantly prolonged survival time and reduced rejection response of heart allografts in vivo, which are involved in downregulation of TNFRSF4 expression. These results provided a novel molecular mechanism of ameliorating heart allograft rejection in Treg cells, which could be used in the treatment of heart allograft rejection clinically.