蜕膜CCR10+调节性T细胞的募集、表型与功能分析

During pregnancy, decidual regulatory T cells (Tregs) expand at the maternal-fetal interface and play an important role in establishment and maintenance of successful pregnancy. However, cells globally termed Tregs are a heterogeneous population. In the previous study, we found there is a decidual CCR10+Treg subset at the maternal-fetal interface and decidual stromal cells express the CCR10 ligand CCL28, levels of which could be up-regulated by pro-inflammatory cytokines. Based on our previous studies, we continue to study CCL28 expression at the maternal-fetal interface of both normal pregnancy and recurrent spontaneous abortion, and make thorough studies into how pro-inflammatory cytokines, pregnancy-related hormones and hypoxia could regulate the expression of CCL28. In our project, chemotaxis assay will be used to investigate the recruitment of CCR10+Tregs by CCL28. Performing with flowcytometry, we will identify the phenotype of a decidual CCR10+Treg population at the maternal-fetal interface. Functional analysis of CCR10+Tregs will be further conducted by establishment of cell co-culture systems. This project proceeds with the recruitment of decidual CCR10+Tregs by CCL28 from the maternal-fetal interface, analyzes the phenotype and function of decidual CCR10+Tregs, and clinically leads to preventive and therapeutic suggestion for recurrent spontaneous abortion.

妊娠期蜕膜局部调节性T细胞（Treg）明显扩增，在妊娠的成功建立和维持中起重要作用，但其表型并不均一。我们前期研究发现蜕膜局部存在一群CCR10+Treg，蜕膜基质细胞表达CCR10配体CCL28，并且其产生受促炎性细胞因子调节。本项目在既往研究基础上，继续研究正常早孕及复发性自然流产母-胎界面功能细胞CCL28的表达及促炎性细胞因子、妊娠相关激素和缺氧等母-胎界面微环境对其的调节；采用趋化模型研究CCL28对CCR10+Treg的募集；使用流式细胞术，鉴定蜕膜CCR10+Treg的表型；建立细胞共培养体系解析CCR10+Treg对效应T细胞的增殖抑制功能和对母-胎界面功能细胞的作用。本研究有助于进一步了解妊娠期母-胎界面Treg优势的形成，鉴定一群新的蜕膜CCR10+Treg亚群，丰富对Treg的认识，为临床上复发性流产等母-胎免疫调节紊乱疾患的防治提供新思路。