LILRA3调控Tfh细胞参与狼疮肾炎发病的免疫学机制研究

狼疮性肾炎（LN）是系统性红斑狼疮最常见和最严重的并发症。滤泡辅助性T（Tfh）细胞在LN致病机制中具有重要作用。课题组前期研究发现：1）野生型LILRA3是LN发病的高风险遗传因素；2）LILRA3在SLE患者表达水平明显升高；3）和非狼疮肾炎相比，LN患者的血清LILRA3水平进一步明显升高。近期课题组进一步发现：在狼疮模型中，人源化LILRA3敲入鼠出现：1）脾脏明显增大；2）脾脏Tfh细胞、生发中心B细胞、浆细胞比例明显增高；3）血清抗双链DNA抗体滴度明显增高；4）肾脏病理呈肾小球内皮细胞增殖样改变。课题组拟进一步探讨LILRA3对Tfh 细胞分化的作用机制，并通过经典狼疮肾炎动物模型，明确LILRA3对LN发病的作用及分子机制。本课题将从分子、细胞、患者和动物模型四个层面，探讨LILRA3对LN的致病作用, 为深入理解LN发病机制提供新线索, 也可能为LN治疗提供新的干预靶点。

Lupus nephritis (LN) is the most common complications of systemic lupus erythematosus (SLE), and it is also the main cause of death in lupus patients. Recently, it has been found that follicular helper T (Tfh) cells play an important role in the pathogenesis of LN. Our previous study found that: 1) Wild-type LILRA3 is a high-risk genetic factor for LN; 2) Expression level of LILRA3 is significantly higher in SLE patients; 3) Compared with non-LN patients, the serum LILRA3 levels in LN patients is further significantly elevated. The data have been published in Annals of the Rheumatic Diseases. We further found that: in the lupus like disease model, the human LILRA3 knock-in mice displayed: 1) Spleen mass significantly increased; 2) Proportions of Tfh cells, germinal center B cells, and plasma cells were significantly increased; 3) Titers of serum anti-dsDNA antibodies were increased significantly; 4) Proliferation of glomerular endothelial cells appeared in renal pathology, suggesting a mild renal damage. Next, we will further investigate the role of LILRA3 in activation of Tfh cells and in the pathogenesis of LN in classical LN animal models.