系统性红斑狼疮（SLE）是一种累及全身多个系统，病程迁延反复的自身免疫性疾病。其中，狼疮性肾炎是最常见、最严重的内脏损伤之一。近年来，多个研究机构报道编码巨噬细胞分化抗原-1（Mac-1）的基因序列ITGAM与SLE易感性有关。而对于SLE的发病机制，涉及到复杂的细胞间相互作用的过程，最近，B细胞的活化成熟及其成熟后产生的抗体影响的作用逐渐引起人们的注意。本项目拟在野生型鼠和Mac-1基因敲除鼠上，利用pristane诱导狼疮性肾炎模型，研究Mac-1对于B淋巴细胞的调节机制。我们前期结果显示Mac-1基因敲出组小鼠在pristane注射6个月以后，狼疮性肾炎疾病更加严重。我们推测Mac-1通过直接调节B细胞凋亡或间接通过B细胞受体（BCR）、B细胞激活因子（BAFF）来调控B细胞的活性，从而参与到狼疮性肾炎的病程中。同时，我们也将评估Mac-1、BAFF是否能成为狼疮性肾炎的治疗靶点。

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with strong genetic and environmental components. Autoantibodies play an important role in the pathogenesis of SLE. Lupus nephritis is one of most common part in SLE. Recently, an association of genetic variations in ITGAM, the gene sequence of macrophage-1 antigen (Mac-1), with susceptibility to SLE has been reported in several genome-wide association studies. The mechanism of SLE is complicated. People think B cell hyperactivity may be important. To determine the underling mechanism of how Mac-1 participates in lupus nephritis, we introduced pristane to induce experimental lupus nephritis in Mac-1-/- mice and WT mice on C57BL/6 background. Our data showed that after 6 months after pristane injection, Mac-1-/- group indicated an enhance disease to compared with WT group. In this program, we hypothesis that Mac-1 may regulate B cell activation and apoptosis via directly or indirectly pathway in lupus nephritis. Meanwhile, we’ll evaluate the possibility for the application of Mac-1 and B-cell-activating factor (BAFF) as a potential clinical therapeutic target in lupus nephritis.