异位灶微环境调节性T细胞的功能调节及其作用机制

项目名称： 异位灶微环境调节性T细胞的功能调节及其作用机制

项目编号： No.81200425

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 王晓秋

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 子宫内膜异位症（简称内异症）以子宫内膜在异位种植、生长为特征，所致的痛经、不孕等严重影响生育期妇女的生殖健康。异位子宫内膜不能被有效清除，提示盆腹腔浆膜免疫功能障碍。我们已研究发现，内异症腹腔内调节性T细胞（Treg）数目增加，且IL-10、TGF-β1的水平升高；同时具有更高水平的趋化因子TECK存在。体外研究表明，雌激素（E2）与二噁英（TCDD）作为内外环境因素协同作用，通过促进子宫内膜间质细胞（ESC）分泌TECK趋化Treg细胞。本研究将通过建立Treg与ESC细胞的共培养体系，应用重组细胞因子或特异性中和抗体，探讨在E2与TCDD作用下，ESC通过分泌TECK介导Treg扩增，调节功能表型及免疫抑制作用；进一步研究Treg对ESC增殖、粘附、侵袭的升调节作用及其分子机制；以解析异位灶微环境Treg免疫抑制功能增强，介导异位内膜的种植与生长的分子机制,最终为内异症防治提供新策略。

中文关键词： 子宫内膜异位症；调节性T细胞；趋化因子；促炎细胞因子；血管形成

英文摘要： Endometriosis,an endocrine and chronic inflammatory disease, is a very frequent gynecological disorder in the fertile phase, which is characterized by ectopic implantation and growth of endometrium.It has seriously affected the reproductive health of fertile women because of dysmenorrhea and infertility. The retrograde menstruation occurs in almost all cycles,suggesting that the onset of endometriosis involves inefficient clearance of the mestrual efflux from the pelvis with the abnormal immune microenvironment in abdominal cavity. Previous work on primates has shown that exposure to the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with an increased prevalence and severity of endometriosis. Our previous work has found that among the endometriosis-associated cells, ESC is the main source of chemokine TECK. We have recently discovered that there is much more regulatory T cells (Treg) and higher IL-10, TGF-β1 in abdominal cavity of endometriosis compared to the non-endometriosis, and there is also higher TECK in pelvic cavity. Our studies in vitro showed that the combination of estradiol with TCDD as internal and external environment factors could promote TECK secretion by ESC which therefore has stronger chemotaxis to Treg. In this project, we will establish Treg-ESC co-culture with recombinant

英文关键词： endometriosis；regulatory T cells；Chemokine；proinflammatory cytokine；vascularization