系统性红斑狼疮(SLE)发病中B细胞过度激活分化形成浆细胞并分泌大量自身抗体，是导致炎症持续存在的重要因素。在狼疮发病进程中，大量浆细胞聚集在靶器官的炎症局部及淋巴组织中，而其分化及调控机理尚不清楚。现有研究发现Th17细胞参与调节了脾脏生发中心的形成。本课题组近期研究发现浆细胞自身高表达IL-17受体，并且IL-17基因缺失的狼疮小鼠体内浆细胞比例和自身抗体水平均明显降低，狼疮肾炎减轻，提示IL-17参与狼疮发病进程中浆细胞功能的维持，促进自身抗体的产生，并加重了自身免疫性炎症反应。为验证这一假说，我们拟开展以下研究:以诱导发病狼疮小鼠和人源化狼疮小鼠为模型，研究IL-17对浆细胞成熟和存活的调控及其分子机制，观察浆细胞在炎症局部的动态分布，并阐明IL-17调控浆细胞功能对SLE发病和炎症反应的影响。本研究的的完成有助于深入理解SLE的免疫病理机制，并为SLE的治疗策略提供了新的线索。

Systemic lupus erythematosus (SLE) is a severe autoimmune disease featured with excessive autoantibody production and multiple organ damage. During SLE progression, accumulated plasma cells in inflamed tissues and lymphoid organs are involved in persistent autoimmune inflammation, but it is largely unclear how plasma cell differentiation is regulated. Current studies have suggested a key role of Th17 in promoting germinal center response and autoantibody production, but little is known about the potential role of IL-17 in plasma cell function. Our pilot studies detected a high level of IL-17 receptor expression on plasma cells. Moreover, IL-17 deficiency resulted in significantly reduced plasma cell frequency, autoantibody production and disease severity in lupus mice. In this proposal, we aim to determine a critical role of IL-17 in regulating plasma cell differentiation and function using both lupus-prone mice and humanized lupus mouse model. The expected findings will provide new insights in understanding the roles of IL-17 and plasma cells in the pathogenesis of SLE.