干燥综合征发病中自身反应性CD11c+B细胞的作用及其调控机制研究

原发性干燥综合征是以自身反应性B细胞活化为主要病理进程的系统性自身免疫疾病，近期研究发现CD11c+B细胞是一群新的自身反应性B细胞并参与多种自身免疫病的发病，但其是否在原发性干燥综合征中具致病作用尚未阐明。我们的前期研究发现实验性干燥综合征小鼠的唾液腺局部存在CD11c+B细胞的大量聚集并分泌自身抗体，而且过继性回输CD11c+B细胞能够直接诱导免疫缺陷型Rag2-/-鼠中干燥综合征的发病，提示唾液腺局部自身反应性CD11c+B细胞参与了靶器官的炎症及组织损伤，而唾液腺局部大量聚集的效应性T细胞则可能介导CD11c+B细胞的分化。为证实这一假说，课题组拟运用原发性干燥综合征小鼠模型研究自身反应性CD11c+B细胞及效应性T细胞的功能及其相互作用的分子机制，并阐明其参与干燥综合征发病的作用机理。

Primary Sjögren’s syndrome (pSS), an autoimmune disease affecting exocrine glands is mainly mediated by activation of autoreactive B cells. Recent studies have suggested the pathogenic functions of CD11c+ B cells in the development of various autoimmune diseases but their role in the pathogenesis of pSS remains largely unclear. Our pilot studies revealed the significant expansion of CD11c+ B cells in salivary gland (SG) of mice with experimental Sjögren’s syndrome (ESS). Importantly, we showed that adoptive transfer of CD11c+ B cells potently triggered ESS development in Rag2-/- recipients. Moreover, the SG local-infiltrated effector T cells might be involved in inducing the differentiation and expansion of CD11c+ B cells during ESS development. In this project, we aim to identify the function of CD11c+ B cells in SG pathology and reveal their underlying cellular and molecular mechanisms in the development of ESS. Furthermore, we will determine the role of SG-infiltrated effector T cells in regulating the differentiation and function of CD11c+ B cells. The expected findings will contribute to the further understanding of a critical role of CD11c+ B cells in ESS pathogenesis and may facilitate the development of new therapeutic strategy for the treatment of pSS.