诱导移植物免疫耐受是移植领域研究的热点。我们前期研究发现，ECDI结合供体脾细胞（ECDI-SP）可以显著延长小鼠移植心脏存活时间，但其机制尚未完全阐明。ECDI-SP在受者体内迅速凋亡，并被脾脏巨噬细胞所吞噬。Mertk/Gas6/ProS1信号通路在巨噬细胞吞噬凋亡细胞，并向M2型巨噬细胞分化中起重要作用。在预实验中，受体小鼠Mertk基因被敲除后，ECDI-SP诱导免疫耐受被阻断，脾脏M2型巨噬细胞显著减少。因此，我们推测巨噬细胞可能通过Mertk/Gas6/ProS1信号通路吞噬ECDI-SP，向M2型巨噬细胞分化，进而诱导移植物免疫耐受。本课题拟从小鼠心脏移植模型和体外细胞实验两方面，探讨Mertk/Gas6/ProS1信号通路在介导巨噬细胞吞噬ECDI-SP中的关键作用，并阐明活化该信号通路促进ECDI-SP诱导移植心脏免疫耐受的分子机制，为临床诱导移植免疫耐受提供新的方法。

Investigation on inducing immune tolerance for allograft is a hot point on transplant field. In our previous study, we found ECDI fixed donor splenocyte (ECDI-SP) could significantly prolong survival time of mice cardiac allograft, however the underlying mechanism still needs to be elucidated. ECDI-SP goes apoptosis rapidly in recipient and is phagocystosis by macrophage in spleen. Mertk/Gas6/ProS1 signal pathway has been shown to have an important role in phagocystosis of apoptosis cells by macrophage and inducing macrophage differentiation to M2 macrophage. In the pilot study, we found immune tolerance induced by ECDI-SP was blocked, and M2 macrophage in spleen significantly decreased when Mertk gene of recipient mice were knocked out. Therefore, we postulate that macrophage may phagocystosis of ECDI-SP by Mertk/Gas6/ProS1 signal pathway, differentiate to M2 macrophage, and then induce immune tolerance of cardiac allograft. In this study, we plan to explore the key role of Mertk/Gas6/ProS1 signal pathway in mediating macrophage phagocystosis of ECDI-SP, and to elucidate the underlying molecular mechanism of activating this pathway to promote ECDI-SP inducing immune tolerance of cardiac allografts in mice heart transplant model and ex vivo cell culture experiment. The aim of this study is to provide new methods for inducing immune tolerance of allograft in clinic.