Foster M H
The Penn Kidney Center, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6144, USA.
Semin Nephrol. 1999 Jan;19(1):12-24.
Systemic lupus erythematosus (SLE) is characterized by spontaneous B and T cell autoreactivity and multiorgan immune injury including severe glomerulonephritis. This autoimmune syndrome results from a global derangement in immune regulation dependent on the interaction of complex genetic and environmental susceptibility factors. Animal models have provided a powerful tool to study disease mechanisms and novel therapeutic interventions under well-defined conditions, and bypass the barriers inherent in the study of human lupus. Classical models of spontaneous and investigator-induced murine lupus, their mutant variants, and novel transgenic and gene-targeted mutant lineages have been particularly useful. Extensive genome typing in inbred and recombinant lupus-prone strains permits mapping and characterization of multiple lupus susceptibility loci and genes and their contribution to various disease phenotypes. Murine models provide important insight into the identity of targeted self-antigens, the molecules and pathways that maintain tolerance, immune cell and cytokine interactions that promote autoimmunity, and mechanisms of renal localization and injury by immune effectors. These models reveal that multiple and independent mechanisms contribute to disease pathogenesis and provide a better understanding of the remarkable phenotypic and histopathologic heterogeneity that characterizes human SLE.
系统性红斑狼疮（SLE）的特征是B细胞和T细胞自发产生自身反应性以及多器官免疫损伤，包括严重的肾小球肾炎。这种自身免疫综合征是由复杂的遗传和环境易感性因素相互作用导致的免疫调节全面紊乱所引起的。动物模型为在明确界定的条件下研究疾病机制和新型治疗干预措施提供了有力工具，并且绕过了人类狼疮研究中固有的障碍。自发性和研究者诱导性小鼠狼疮的经典模型、它们的突变变体以及新型转基因和基因靶向突变谱系都特别有用。对近交和重组狼疮易感性品系进行广泛的基因组分型，有助于绘制和鉴定多个狼疮易感基因座和基因，以及它们对各种疾病表型的贡献。小鼠模型为深入了解靶向自身抗原的特性、维持耐受性的分子和途径、促进自身免疫的免疫细胞和细胞因子相互作用，以及免疫效应器在肾脏中的定位和损伤机制提供了重要线索。这些模型表明，多种独立机制参与了疾病的发病过程，并且有助于更好地理解人类SLE所特有的显著表型和组织病理学异质性。
