Inhibition of miR-let-7i Induces DC Immature Cells and Improves Skin Graft Tolerance

Abstract

Dendritic cells (DC) initiate the immune response in the body. They can stimulate T cell activation, proliferation, and differentiation and ultimately participate in the immune response and the immune tolerance response. The purpose of this study was to coculture DCs and T cells and subcutaneously inject DCs transfected with miR-let-7i into rhesus monkey transplantations to verify the role of miR-let-7i in allograft immune tolerance. In vitro studies found that the expression of miR-let-7i was upregulated after inducing the maturation of DCs. The low expression of miR-let-7i inhibited the maturation of DCs, promoted the differentiation of T cells into T helper T cells 2 (Th2), and inhibited T helper T cell 1- (Th1-) driven rejection. In vivo studies also obtained similar results, and subcutaneous injection of DCs transfected with miR-let-7i inhibitor prolonged the survival time of allogeneic skin transplantation. Therefore, we conclude that inhibition of miR-let-7i inhibits DC maturation and improves the tolerance of grafted skin.

Inhibition of DAI refrains dendritic cells from maturation and prolongs murine islet and skin allograft survival

“…DCs are the most potent antigen-presenting cells (APCs), and mature DCs (mDCs) present antigens to CD4 + and CD8 + T cells in class I or II MHC, thus inducing potent T cell responses. On the contrary, immature dendritic cells (imDCs) usually show a high endocytosis capacity and low T cell activation potential, displaying the characteristics of tolerogenic DCs (tolDCs) (5)(6)(7). Therefore, maintaining the immature state of DCs is essential for improving allograft survival.…”