Neuroplastin(NP)是一种单链跨膜糖蛋白黏附分子，临床研究显示NP与精神病、阿尔茨海默病、心脏病、中风、癌症等发生有紧密联系。其亚型NP65异常可导致焦虑样症状、细胞钙离子流动障碍、T细胞分化异常等。本课题组前期研究显示NP65KO小鼠腹腔硫胶质刺激后脾脏明显增大，重量增加，单位质量组织中细胞数却无明显变化，腹腔灌洗液中巨噬细胞和中性粒细胞数较野生型显著减少，骨髓巨噬细胞（BMDM）划痕迁移显示细胞迁移能力明显减弱。采用高通量测序对BMDM基因表达谱分析，差异表达基因933个，参与信号转导基因296个，主要涉及巨噬细胞发育、迁移、溶酶体形成、抗原提呈等，提示NP65KO影响巨噬细胞功能。本研究将从分子表达、细胞功能变化和动物感染模型三个层面探讨NP65对巨噬细胞及相关免疫应答的影响，拟阐明NP65在巨噬细胞和早期免疫应答中的重要作用，为临床NP65异常患者预后评估提供实验依据。

Neuroplastin (NP) is a single-chain transmembrane glycoprotein adhesion molecule. Clinical studies have shown that NP is closely related to psychosis, Alzheimer's disease, heart disease, stroke and cancer. Mutation in NP65 subtype may lead to anxiety-like symptoms, calcium flow disorders in the cell, abnormal T cell differentiation, etc. Previous studies in our group showed that the size and weight of spleen were significantly increased after NP65KO mice intraperitoneal stimulation with thioglycollate medium (TG), but there was no significant change in the number of cells per unit mass tissue. The number of macrophages and neutrophils in peritoneal lavage fluid of NP65KO mice was significantly reduced compared with that of the wild type mice after TG stimulation. The cell migration ratio of bone marrow derived macrophages (BMDM) from NP65KO mice was significantly reduced compared with that of the wild type mice. High throughput sequencing was used to analyze BMDM gene expression profiles. Compared with wild type BMDM, there are 933 genes differentially expressed, 296 of which were involved in signal transduction which mainly involved in macrophage development, migration, lysosome formation, antigen presentation, and so on. These results speculate that NP65KO may affect the function of macrophages and innate immune response. This study will explore the effects of NP65 on macrophages and related immune responses from three aspects: molecular expression levels, cell functional changes and the infectious response in animal model. This project endeavor to elucidate the important role of NP65 in macrophages and early immune responses, and provide experimental basis for prognostic evaluation of patients with abnormal NP65.