系统性红斑狼疮（sisytemic lupus erythematosus,SLE）是以多系统损害为主要表现的自身免疫性疾病。凋亡细胞清除缺陷是导致SLE发病的主要机制。近来研究发现LC3相关吞噬（LC3-associated phagocytosis，LAP）缺陷，而不是经典自噬，可能导致SLE发病。前期研究发现Rab33a低表达抑制巨噬细胞中LAP的产生，也初步证实同dsDNA低的病人相比，dsDNA高的SLE病人单核巨噬细胞Rab33a的表达下调，提示Rab33a可能通过LAP途径调节巨噬细胞吞噬凋亡细胞的能力和抗炎功能。为了证实这一假设，我们拟开展如下研究：以敲除Rab33a的巨噬细胞为模型，分析Rab33a调控LAP的具体环节及分子机制；以巨噬细胞特异性敲除Rab33a基因小鼠为模型和SLE病人为研究对象，探讨Rab33a对巨噬细胞活化和分化的影响，及其在SLE发病中的重要作用。

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple system damage. Defective clearance of apoptotic cells is the main mechanism leading to SLE. Recent studies have found that LC3-associated phagocytosis (LAP) defects, rather than classical autophagy, may contribute to the pathogenesis of SLE. Previous studies have found that low expression of Rab33a inhibits the production of LAP in macrophages, which has preliminarily confirmed that, compared with patients with low dsDNA, the expression of Rab33a in mononuclear macrophages of SLE patients with high dsDNA is down-regulated, suggesting that Rab33a may regulate the ability of macrophages to phagocyte apoptosis cell and anti-inflammatory function through the LAP pathway. In order to confirm this hypothesis, we plan to carry out the following research: taking macrophages knockout Rab33a as the model, analyze the specific links and molecular mechanism of Rab33a regulating LAP; Taking Rab33a gene knockout mice by macrophages as the model and SLE patients as the object of study, the effects of Rab33a on the activation and differentiation of macrophages and its important role in the pathogenesis of SLE were discussed.