BST-2调控糖酵解在舍格伦综合征B细胞体液免疫应答中的机制研究

异常的B细胞体液免疫应答是舍格伦综合征（SS）发病最显著的特征之一，但其发生机制和潜在干预手段尚不明确。分子水平上，活化的B细胞在响应外界信号参与免疫应答时，需要大量的能量供给，其主要来源依赖于糖代谢，尤其是糖酵解的大幅上调。我们先前研究发现，抑制糖酵解能缓解SS发病和异常的体液免疫应答。通过芯片筛选和定位，我们发现BST-2是参与SS发病和体液免疫应答的重要分子，并利用质谱测序等预实验发现BST-2可能与GLUT3存在互作，调控B细胞糖酵解。为此，本研究拟首先研究BST-2调控糖酵解在B细胞体液免疫应答中的作用；随后利用IP、激光共聚焦共定位等方法明确BST-2调控GLUT3等因子介导糖酵解的具体分子机制；最后构建相关动物模型，观察干预BST-2对缓解B细胞异常体液免疫应答及治疗SS的潜在疗效。本项目的开展有望发现SS发病的新机制并转化应用于临床，为提升SS诊断及治疗提供科学依据。

Abnormal humoral immune response is one of the most significant hallmark of Sjögren's syndrome (SS), but the mechanism and the potential therapeutic methods that targets abnormal humoral immune response by B cells remains to be explored. On the molecular levels, the process of activated B cells in responded to externals and product the antigen requires massive energy support. These energies rely on the metabolic state of glucose, especially elevated levels of glycolysis. Our previous studies identified that inhibition of glycolysis an alleviate the progress of SS in animal models, as well as attenuated abnormal humoral immune response. Through high-throughput profiling and sub-size location, we identified that the anti-viral membrane protein BST-2 might act as an important molecular involved in both the development of SS and glycolysis regulation. Therefore, this research firstly aims to investigate the function of BST-2 in regulating glycolysis and B cell humoral immune response. Second, we aimed to explore the molecular mechanism of BST-2 in the maintenance of GLUT3 and other glycolytic factors in B cells. Lastly, we intended to construct BST2(-/-) mice models, and examine the in vivo effectivity of BST-2 to the attenuation of SS symptoms and B cell humoral immune response. The promotion of this research could explore the novel mechanism of SS pathogenesis and transform them into clinical use, thereby supporting the diagnosis and treatment of SS.