Siglec-E在滋养层细胞浸润中的调控作用研究

项目名称： Siglec-E在滋养层细胞浸润中的调控作用研究

项目编号： No.31201082

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 发育生物学与生殖生物学

项目作者： 马芳

作者单位： 四川大学

项目金额： 24万元

中文摘要： 母体子宫内膜免疫系统对胎盘滋养层细胞的识别、容受及调控，是早期胚胎植入的重要过程，但其机理尚不明了。唾液酸结合免疫球蛋白类凝集素（Siglecs）参与的免疫效应调节主要为抑制效应，我们发现：Siglec-E和唾液酸在小鼠子宫蜕膜的自然杀伤细胞（uNK）高表达，已知uNK是蜕膜中与滋养层细胞紧密接触的主要淋巴细胞（占90％）；而且在滋养层细胞亦高表达唾液酸。基于此，我们提出假说：uNK表面的Siglec-E通过顺式结合自身表面的唾液酸，或反式结合与其邻近的滋养层细胞表面的唾液酸，从而激活uNK胞内的免疫抑制效应信号转导途径，降低其细胞毒性；同时诱导滋养层细胞的胞内信号传递系统调节，保证其精确与有序的浸润能力。本课题拟通过研究Siglec-E与唾液酸在蛋白质和细胞水平的结合能力，进一步研究其诱导的uNK免疫抑制效应和对滋养层细胞浸润能力的调节机理。目的是为胚胎植入理论提供新的研究视角和靶点。

中文关键词： 唾液酸结合免疫球蛋白样凝集素-E/7;；宫蜕膜的自然杀伤细胞；滋养层细胞；免疫抑制效应；

英文摘要： Siglecs(sialic acid binding Ig-like lectin) are involved in the inhibitory immune response through the binding with sialic acid on the cell surface, and the maternal endometrial mucosal immune system is associated with the invasion of embryonic trophoblasts for the succesful implantation. We identified there was high expression of Siglec-E and α2-8-linked sialolyglycoconjugates on the mouse uterine natural killer(uNK) which is closely adjacent with trophoblasts and 90% of the lymphocytes in the microenviroment of the uterine mucosa during early pregnancy, also, high expression of α2-3/6 linked sialolyglycoconjugates on the trophoblasts. Based on the preliminary data, we proposed the hypothesis: Siglec-E on uNK might play a key role during the trophoblast invasion via binding with sialic acid on itself and the adjacent trophoblasts, which could activate the signal transduction of inhibitory immune response, simultaneously, mediate the capacity of the trophoblast invasion to avoid the maternal rejection against the embryo and guarantee the precise invasion of trophoblasts. In this study, we plan to explore the specificity of Siglec-E binding with sialic acid, the effect of Siglec-E on the inhibitory reaction and low cytotoxicity of uNK and the trophoblast invasion, which might give us some insights into the expla

英文关键词： Siglec-E/7；uNK；Trophoblast；Immunosuppressive effect；