Rogers Nicola Jane, Lees Mark Jeffrey, Gabriel Luisa, Maniati Eleni, Rose Sarah Jane, Potter Paul Keith, Morley Bernard John
Immunology Department, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK.
J Immunol. 2009 Feb 15;182(4):1982-90. doi: 10.4049/jimmunol.0801320.
Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the production of numerous antinuclear autoantibodies and inflammatory mediators. The BXSB mouse strain is an excellent model of the disease. Previous work has determined a number of important disease susceptibility intervals that have been isolated in separate congenic strains. Here, we have combined expression data from those strains with functional analyses to demonstrate that reduced expression of the innate scavenger receptor Marco (macrophage receptor with collagenous structure) is a primary event in BXSB mice, that reduced mRNA expression is mirrored at the protein level, and that this results in a significant alteration in function. We have confirmed a role for Marco in the clearance of apoptotic cells and a generalized defect in both endocytosis and phagocytosis. The failure to clear apoptotic cells has previously been linked to the development of systemic lupus erythematosus. However, the use of congenic mice with limited phenotypes in this study has enabled us to propose that in the case of Marco at least, disease results from the production of anti-dsDNA Abs.
系统性红斑狼疮是一种多系统自身免疫性疾病，其特征是产生大量抗核自身抗体和炎症介质。BXSB小鼠品系是该疾病的一个优秀模型。先前的工作已经确定了许多重要的疾病易感性区间，这些区间已在单独的同源品系中分离出来。在这里，我们将这些品系的表达数据与功能分析相结合，以证明天然清道夫受体Marco（具有胶原结构的巨噬细胞受体）的表达降低是BXSB小鼠中的一个主要事件，mRNA表达降低在蛋白质水平上也有体现，并且这导致了功能的显著改变。我们已经证实了Marco在凋亡细胞清除中的作用以及在内吞作用和吞噬作用方面的普遍缺陷。未能清除凋亡细胞先前已与系统性红斑狼疮的发展相关联。然而，在本研究中使用具有有限表型的同源小鼠使我们能够提出，至少就Marco而言，疾病是由抗双链DNA抗体的产生导致的。
