致病性MDSCs通过调控B细胞应答参与小鼠实验性干燥综合征的机制研究

原发性干燥综合征（pSS）是一种以进行性炎症和唾液腺、泪腺损伤为特征的自身免疫性疾病。髓源性抑制细胞（MDSCs）是一群具有免疫抑制能力的未成熟髓系细胞。前期研究发现：在小鼠实验性干燥综合征（ESS）模型中，存在一群CXCR5+MDSCs，该细胞能够进入B淋巴滤泡，直接调控B细胞的活化和增殖。因此，我们提出假说：CXCR5+MDSC通过促进B细胞应答参与pSS的发生发展。本项目主要研究：1、CXCR5+MDSCs对ESS疾病进程的作用；2、CXCR5+MDSCs对B细胞存活、增殖、分化和趋化的作用；3、CXCR5+MDSCs调控B细胞应答的分子机制；4、调控CXCR5+MDSCs细胞分化形成的分子机制；5、pSS患者体内CXCR5+MDSCs与疾病和B细胞应答的相关性。本项目将深入阐释CXCR5+MDSCs在pSS中的作用，为靶向MDSCs治疗pSS提供理论依据，开拓新的思路和策略。

As a systemic autoimmune disease, primary Sjögren’s syndrome (pSS) is characterised by progressive inflammation and tissue damage of salivary glands and lacrimal glands. Myeloid-derived suppressor cells (MDSCs) is a population of immature myeloid cells with suppressive capability. Our previous work has found a subset of CXCR5+MDSCs in mice with experimental Sjögren’s syndrome (ESS), and this cell population could localize in B-cell follicles, and promote the activation and proliferation of B cells. Thereafter, we propose the hypothesis: in ESS, CXCR5+MDSCs can enhance the B cell responses and promote the progression of the disease. This project mainly focuses on:(1) the role of CXCR5+MDSCs in ESS development; (2) the regulation of CXCR5+MDSCs on the survival, proliferation, differentiation and chemotaxis of B cells; (3) the molecular mechanism for the regulation of CXCR5+MDSCs on B cells; (4) the molecular mechanism for the differentiation of CXCR5+MDSCs; (5) the correlation between CXCR5+MDSCs and B cell responses in patients with pSS. This project will further elucidate the role of MDSCs in pSS, and providing theoretical basis and novel strategies for the treatment of pSS by targeting MDSCs.