原发性干燥综合征LncRNANR_026938对Tfh细胞Unc5cl/ NF-κB通路调控机制研究

项目名称： 原发性干燥综合征LncRNANR_026938对Tfh细胞Unc5cl/ NF-κB通路调控机制研究

项目编号： No.81501397

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： 郭杰

作者单位： 中国人民解放军第二军医大学

项目金额： 18万元

中文摘要： 原发性干燥综合征（pSS）患者Tfh细胞表达和功能异常，但其具体作用机制不明。本研究组通过mRNA及LncRNA表达谱芯片筛选并验证发现，pSS患者Tfh细胞中LncRNA NR_026938表达显著增高，且其预测靶基因Unc5cl表达呈正相关；体外实验进一步验证发现，Unc5cl通过NF-κB通路调控Tfh细胞表达CXCR5、ICOS等辅助B细胞成熟和维持异位生发中心形成的重要分子。本项目拟研究以下科学问题：1、LncRNA NR_026938对Tfh细胞数量和功能紊乱的调控机制；2、甲基化或转录因子等对LncRNA NR_026938在Tfh细胞表达的调控机制；3、利用pSS小鼠动物模型，探讨调节LncRNA NR_026938治疗和预防pSS的可能性。通过以上研究，将有助于阐明pSS中LncRNA NR_026938对免疫应答的调控机制，为探讨pSS免疫干预治疗提供新的靶点。

中文关键词： 原发性干燥综合征；滤泡辅助性T细胞；Unc5cl；NF-κB；长链非编码RNA

英文摘要： Primary Sjögren's syndrome (pSS) patients have abnormal Tfh cell expression and function , and the specific mechanism remains elusive. Previous studies showed significantly higher expression of LncRNA NR_026938 in pSS patients by microarray screening of mRNA and LncRNA, and verified it and its positive correlation with the expression of predicting target gene- Unc5cl ; experiments in vitro further verified that Unc5cl can activate NF-κB pathway, result in Tfh cells expressing CXCR5, ICOS and other important molecular, which assist B cell maturation and the maintenance of ectopic germinal center . Therefore, this project intends to solve the following scientific problems: 1. The mechanisms of LncRNA NR_026938 regulating quantity and function of Tfh cell; 2. The regulatory mechanisms of methylation or transcription factors in the expression of LncRNA NR_026938 in Tfh cells; 3. Using a pSS mice model to explore the possibility of regulationg LncRNA NR_026938 for the treatment and prevention of pSS. Through these studies, it will help us to clarify the regulatory mechanism of LncRNA NR_026938 in immune response of pSS , and provide new targets for pSS therapeutic intervention.

英文关键词： primary Sjögren's syndrome ;T follicular helper cell;Unc5cl;NF-κB;long non-coding RNA