IL-25信号通路及其在溃疡性结肠炎中的作用机制研究

项目名称： IL-25信号通路及其在溃疡性结肠炎中的作用机制研究

项目编号： No.31470887

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 康自珍

作者单位： 上海交通大学

项目金额： 90万元

中文摘要： 溃疡性结肠炎（溃结）是炎性肠病的一种，其发病率近年来在我国呈上升趋势。已有的研究表明II型免疫反应在溃结的病理发生中起重要作用，但是关于其II型免疫反应产生的机制仍不清楚。IL-25是IL-17家族一员，是II型免疫反应的主要驱动者之一。我们的前期研究通过寄生虫感染的动物模型，发现上皮细胞来源的IL-25通过作用于上皮细胞形成一个IL-25产生的正反馈循环。IL-25诱导上皮细胞产生IL-25和IL-33，IL-25和IL-33 诱导II型固有淋巴样细胞的扩增，进而诱发II型免疫反应。然而，IL-25的信号转导途径及其在溃结中的作用机制目前还不知道。本项目假设IL-25在溃结的II型免疫反应中发挥重要作用。我们将通过动物模型、病人样品和以II型固有淋巴样细胞为细胞模型来研究IL-25诱导的信号通路及其在溃结中的作用机制。这一研究将为溃结的治疗提供新的思路。

中文关键词： ；IL-25信号通路；溃疡性结肠炎；固有淋巴样细胞；II；型免疫反应

英文摘要： The incidence of inflammatory bowel disease (IBD) is increasing in China with urbanization and socioeconomic development. Population-based IBD epidemiological study in Guangdong of China suggests the incidence of IBD is similar to that in Japan and Hong Kong but lower than that in South Korea and Western countries. Uncerative colitis(UC) is one of the chronic IBD without a medical cure and with unknown etiology. Current research suggests that type 2 response is a major reason for the pathogenesis of UC. The most divergent member of the IL-17 family is IL-17E (IL-25); it is induced in airway epithelial cells in response to allergens, expressed in mouse T lymphocytes of the CD4+ subset with a Th2 cell profile and human innate effector eosinophils and basophils. IL-25 has been demonstrated as one of the major driver of type 2 responses,implicating in allergy, asthma and helminth immunity.We previously examined the cell-type specific role of IL-25-induced Act1-mediated signaling in protective immunity against helminth infection. We found that targeted Act1 deficiency in epithelial cells resulted in a marked delay in worm expulsion and abolished the expansion of the Lin-c-kit+ innate cell population in the mesenteric lymph node, lung and liver. Our results suggest that epithelial-specific Act1 mediates the expansion of the Lin-c-kit+ innate cell population through the positive feedback loop of IL-25, initiating the type 2 immunity against helminth infection. However,the role of IL-25 signaling in the pathogenesis of UC remains unknown. We thus hypothesize that IL-25 signaling is critical for the initiation of type 2 response in UC and for the pathogenesis of the disease. We'll test our hypothesis by using animal model of UC, UC patient samples and innate lymphoid cells as well. This study is to define the roles of IL-25 signaling in the pathogenesis of UC, thus may provide new therapeutic strategies for UC in the future.

英文关键词： IL-25 signaling;Ulcerative Colitis;type 2 response;Innate lymphoid cells