CD155促进滋养细胞侵袭及通过TIGIT/CD226调控Treg功能的机制研究

母胎界面调节性T细胞（Treg）功能异常、滋养细胞侵袭不足均可导致流产。申请人前期发现复发性自然流产（RSA）患者Treg表面共抑制受体分子TIGIT降低，与共刺激分子CD226的比例失调，滋养细胞上配体CD155表达下降；封闭CD155可抑制滋养细胞侵袭。提示CD155可能具有调控滋养细胞侵袭和通过TIGIT/CD226调控Treg功能的双重作用，但具体机制未明。本项目拟通过分析RSA患者及正常早孕者外周及母胎界面TIGIT/CD226与CD155信号分子的表达及作用，结合流产小鼠模型，探究TIGIT/CD226竞争性结合CD155对Treg增殖、凋亡、表达功能因子及免疫抑制能力的调节作用；揭示CD155激活滋养细胞FAK/Src/ERK信号通路促进其侵袭的机制；明确干预相关信号对妊娠结局的影响。以期阐明CD155促进滋养细胞侵袭及调控Treg功能的机制，为RSA的诊治提供新的思路。

Abnormal function of regulatory T cells (Treg) and insufficient invasion of trophoblast cells at maternal-fetal interface can lead to abortion.The applicant previously found that in patients with recurrent spontaneous abortion (RSA), the co-inhibitory receptor molecule TIGIT was reduced on the surface of Treg, and the ratio of co-stimulatory molecule CD226 to TIGIT was out of proportion, and the expression of ligand CD155 on trophoblast cells was decreased. Blocking CD155 could inhibit trophoblast cell invasion.These results suggest that CD155 may play a dual role in regulating trophoblast invasion and regulating Treg function through TIGIT/CD226 signal, but the specific mechanism remains unclear.This project intends to explore the regulatory effects of CD155 by competitive combination with TIGIT/CD226, on proliferation, apoptosis, expression of cytokines and immunosuppressive ability of Treg. We analysed the expression and role of TIGIT/CD226 and CD155 signal molecules at the peripheral and maternal-to-fetal interface of RSA patients and normal early pregnant women, and verified with the aborted mouse model. To reveal the mechanism of CD155 activating the trophoblast cell FAK/Src/ERK signaling pathway to promote its invasion, and to determine the impact of intervention-related signals on pregnancy outcomes. In order to clarify the mechanism of CD155 promoting trophoblast invasion and regulating Treg function, and provide a new insight for the diagnosis and treatment of RSA.