IL-27通过诱导异位灶微环境IL-10+Th17细胞分化促进内异症进展的分子机制

项目名称： IL-27通过诱导异位灶微环境IL-10+Th17细胞分化促进内异症进展的分子机制

项目编号： No.81471513

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李明清

作者单位： 复旦大学

项目金额： 74万元

中文摘要： 研究显示子宫内膜异位症（简称内异症）患者盆腹腔局部免疫微环境异常，不仅不能清除异位灶内膜间质细胞（ESC）且促进其生长种植。近来研究提示IL-10+Th17细胞具有调节功能。我们发现内异症患者腹腔液存在高水平Th17细胞及IL-17A，III-IV期患者有更高水平IL-10，提示随疾病进展，呈现促炎和耐受并存并偏向耐受的过程。我们新近发现异位灶ESC高表达IL-27，与巨噬细胞共培养后可诱导naive T向IL-10+Th17细胞分化，但分子机制及其在内异症发展中的作用尚不清楚。故本课题以体外模拟内异症盆腹腔微环境和体内动物实验为研究手段，拟研究ESC和巨噬细胞来源的IL-27通过何种信号和下游转录因子介导这群Th17细胞分化，进一步解析这群细胞是否通过IL-17A和IL-10促进内异症进展及病理机制。本课题将为内异症发病机理研究提供新的研究方向，为寻找防治内异症的新策略提供科学依据。

中文关键词： 白细胞介素27；异位灶微环境；IL-10+Th17细胞；子宫内膜异位症；分子机制

英文摘要： It has been reported the abnormal local immune microenvironment in abdominal from women with endometriosis can not effectively remove endometrial stromal cells (ESC) of the ectopic foci.In contrast, it can promote the growth and implantation of ESC. Recent studies suggest that IL-10+Th17 cells have regulatory function. We found that the peritoneal fluid (PF) of patients with endometriosis had high levels of Th17 cells and IL-17A. Moreover, IL-10 level of PF in III-IV patients was higher than that in I-II patients. The results suggested that the local microenvironment of women with endometriosis present a coexistence state of pro-inflammatory and tolerance. The initial stage of this disease, a dominant position is pro-inflammatory. On the contrary, such advantage tends to tolerance during the latter of endometriosis. Further studies showed that ESC of ectopic foci highly expressed IL-27. After co-culture with macrophage, it could induce na?ve T differentiate to IL-10+Th17 cells. However, the molecular mechanisms and the roles in the development of endometriosis are unclear. Therefore, takeing advantege of in vitro trials for imitating the abdominal microenvironment in endometriosis and in vivo animal experiments, our study intends to investigate the downstream signal pathways and transcription factors which are involved in ESC and macrophage-derived IL-27 on IL-10+Th17 cells differentiation, to further explore whether these Th17 cells promote the progress of endometriosis by secreting IL-17A and IL-10, and to study the pathological mechanisms.This project will provide a new direction for researching the pathogenesis of endometriosis, and the scientific basis for finding new strategies in the prevention and treatment of endometriosis.

英文关键词： IL-27;the ectopic foci microenvironment;IL-10+Th17 cells;endometriosis;molecular mechanism