NPSR1在小鼠结肠炎中对CD4+T淋巴细胞调控作用的研究

Although the precise etiology of inflammatory bowel disease (IBD) has not yet been elucidated, extensive studies have revealed the importance of CD4+ T lymphocytes in IBD pathogenesis. Our previous research identified NPSR1 as a susceptibility gene for IBD in Chinese Han population, found that the expression of NPSR1 was enhanced in intestinal mucosa of IBD patients compared to healthy controls, and revealed a close connection between NPSR1 and CD4+ T cells. However, the way of how NPSR1 regulates the functions of CD4+T cells and participates in the pathogenesis of IBD remains unclear. Based on an acute TNBS colitis model in Balb/c mice and a chronic CD4+CD45high T-cell transfer colitis model in C57BL/6 mice, using siRNA interference in vivo, this study aims to explore the influences of NPSR1 down-regulation in intestine on the phenotypes of mice in the above models, and confirm the impacts of NPSR1 on the functions of CD4+ T cells such as cell differentiation, chemotaxis, apoptosis, proliferation and its contact with some kind of innate immune cells in vivo and vitro. Clarifying these speculations will help extending our understanding about the role of NPSR1 in the pathogenesis of IBD, and will be powerful evidence and important theoretical basis of whether NPSR1 can be taken as a new therapeutic target for IBD.

炎症性肠病(IBD)发病机制尚未明晰，大量研究提示CD4+T细胞在IBD的发生发展中有重要作用。申请者前期研究发现神经肽S受体1(NPSR1)基因多态性与中国汉族人群IBD易感性相关，且其在IBD患者肠道表达升高，其功能可能与CD4+T细胞有密切关联。但NPSR1如何通过调控CD4+T细胞继而参与IBD的发病机制仍不清楚。本研究拟通过构建急性Balb/c小鼠TNBS结肠炎模型及慢性C57BL/6小鼠CD4+CD45highT细胞过继转移肠炎模型，采用活体内siRNA干扰技术，观察下调肠道NPSR1的表达对小鼠肠炎表型的影响，明确在小鼠肠炎中NPSR1对CD4+T细胞分化、趋化、凋亡、增殖以及其与天然免疫细胞之间的联系等功能的影响。阐明这些问题将有助于扩展我们对NPSR1参与IBD发病具体机制的理解，并为探寻能否将NPSR1作为新的IBD治疗靶点提供直接证据和重要的理论依据。

炎症性肠病(IBD)发病机制尚未明晰，大量研究提示CD4+T细胞在IBD的发生发展中有重要作用。申请者前期研究发现神经肽S受体1(NPSR1)基因多态性与中国汉族人群IBD易感性相关，且其在IBD患者肠道表达升高，其功能可能与CD4+T细胞有密切关联。但NPSR1如何通过调控CD4+T细胞继而参与IBD的发病机制仍不清楚。本研究拟通过构建慢性C57BL/6小鼠DSS肠炎模型，采用活体内siRNA干扰技术，观察下调肠道NPSR1的表达对小鼠肠炎表型的影响，明确在小鼠肠炎中NPSR1对CD4+T细胞分化和趋化功能的影响。本项目已发表论文两篇，NCBI和Web of Science皆可查询，具体信息见研究成果一栏，目前实验结果主体论文还在撰写中。成果主要可运用于生物科学领域，为探寻是否可以将NPSR1作为新的IBD治疗靶点提供直接证据和重要的理论依据。本项目明确了NPSR1可作为IBD免疫治疗的潜在靶点，这一观点仍需要更多临床实践以及实验加以证实。