变应性鼻炎孕母暴露PM2.5对子代脐血Th2细胞亚群极化影响及其表观遗传调控研究

项目名称： 变应性鼻炎孕母暴露PM2.5对子代脐血Th2细胞亚群极化影响及其表观遗传调控研究

项目编号： No.81502815

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李幼瑾

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 变应性鼻炎（AR）是儿童最常见慢性疾病之一，发病率日趋增高，其中环境因素可能是重要原因。研究发现PM2.5是儿童AR发生的独立风险因素，并与其IFN-γ基因启动子甲基化异常相关。鉴于IFN-γ启动子异常甲基化可能是造成AR中Th2细胞亚群极化状态的重要因素，而此极化状态在AR易感患儿的脐带血中已存在。由此我们推测孕期PM2.5暴露可能改变IFN-γDNA甲基化水平来加重脐带血Th2细胞亚群极化状态，而影响子代AR发病的作用机制。本研究拟通过建立规范的600对母婴出生队列，采用个体PM2.5暴露评估，重点考察AR母亲孕期PM2.5暴露的时间和浓度对其子代AR发生的影响，观察子代脐带血中Th2细胞亚群极化状态，追踪儿童AR发生趋势并采集相关生物标本，分析IFN-γDNA甲基化水平与改变婴幼儿Th2细胞亚群极化状态之间的表观遗传调控机制。若上述工作假设得以证实，将为AR的早期预防提供新视角。

中文关键词： 孕期；变应性鼻炎；PM2.5；Th2亚群极化；DNA甲基化

英文摘要： Allergic Rhinitis(AR)，a chronic inflammatory disease in children, has high prevalence in children due to the impact of environment. PM2.5 has been proved to an independent risk factor for AR in children and related with abnormal level of IFN-γ methylation in promoter in our preliminary work. Meanwhile elevated Th2 cells in cord blood were of relevance with AR-like infants which have maternal allergic history. It was believed that Th2 skewing contributed to incidence of AR. We hypothesize that PM2.5 exposures during pregnancy may induce accentuation of Th2 skewing via abnormal of IFN-γ methylation in promoter and affect development of future AR in offspring. We propose to recruit 600 prospective mothers in their first trimester of otherwise uncomplicated singleton pregnancies. Maternal allergic history, total serum IgE and estimated exposure of PM2.5 were collected. Mother peripheral blood samples and cord blood were obtained and assayed for the level of IFN-γ methylation. AR-like symptom and other atopy will be periodically assessed during the first 2 years of life for the aim to reveal the etiology and prevention of AR.

英文关键词： pregnancy;allergic rhinitis;PM2.5;Th2 skewing;DNA methylation