移植排斥和难以诱导特异性免疫耐受是心脏移植治疗的主要瓶颈。树突状细胞(DC)，尤其是未成熟树突状细胞可通过诱导和扩增调节性T细胞（Treg）诱导免疫耐受。近年发现miRNA可参与DC分化、成熟及功能的调控，申请者前期体外研究证实miR-let-7i与DC成熟及Treg增殖有关，但其具体机制尚不明确。本研究拟在前期工作基础上，主要探讨DC中miR-let-7i是否可通过靶向SOCS1调控TLR4/MAL-NF-κB信号通路影响DC功能；阐明miR-let-7i对Treg、Th1/Th2间平衡的调控及机制；并在大鼠心脏移植模型中回输由miR-let-7i处理的CD86-DC，探讨是否可诱导移植免疫耐受，从而验证体外研究的结果及机制。本研究首次探讨通过靶向抑制miR-let-7i来调控DC成熟，达到诱导心脏免疫耐受并阐明其机制，该研究将为临床心脏移植的免疫耐受诱导奠定基础并提供新的治疗思路。

Heart transplantation is an effective treatment for end-stage heart disease，however,the difficulty in immune-tolerance induction and rejection of transplant graft which greatly limit heart transplantation development. In recent years, several evidences showed that miRNA involved in DCs maturation regulation, but little is known about miRNA function involved in the induction heart transplant immune tolerance. Our group focus on the treatment of heart transplantation rejection for many year,and made some progresses about the DCs function in the induction of immune tolerance.We firstly found that, in vitro transfection of miR-let-7i inhibitor can inhibit DCs maturation, and the target is SOCS1. The CD86-DCs separated by immune-magnetic bead could induce Treg proliferation. Though we already have the evidence of the miR-let-7i could regulate DCs function, induce Treg proliferation,the elaborate mechanism is not clear. Therefore, we aims to reveal the mechanism of miR-let-7i regulate the the DCs functions. Our hypothesis is miR-let-7i regulate the functional status of DC via targeting SOCS1-TLR4/MAL-NF-κB signaling pathway and induce Treg proliferation and Th1/Th2 balance.Meanwhile, in order to confirm miR-let-7i inhibitor treated CD86 -DC could induce immune tolerance in vivo, we set up a heart transplantation model, and evaluates the effect of miR-let-7i in transplantation immune tolerance by infusion with the miR let-7i inhhibitor treated CD86-DC. This subject may help to clarify the mechanisms of miR-let-7i regulate DC maturation status and induced heart transplantation immune tolerance, which provide a new perspect of immune tolerance.