Zhuang Haoyang, Szeto Christopher, Han Shuhong, Yang Lijun, Reeves Westley H
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida , Gainesville, FL , USA.
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL , USA.
Front Immunol. 2015 Jun 5;6:291. doi: 10.3389/fimmu.2015.00291. eCollection 2015.
Human lupus is strongly associated with a gene expression signature characterized by over-expression of Type I interferon-regulated genes. A strong interferon signature generally is not seen in the standard mouse models of lupus, despite considerable evidence for the involvement of toll-like receptor-driven interferon production. In contrast, pristane-induced lupus exhibits a prominent TLR7-dependent interferon signature. Importantly, genetic disorders with dysregulated interferon production in both human beings and mice cause severe autoinflammatory diseases but not the typical manifestations of lupus, suggesting that interferon over-production is insufficient to cause systemic lupus erythematosus itself. Single-gene models in mice suggest that lupus-like disease may result from abnormalities in B-cell activation and the clearance of dead cells. Pristane may mimic human systemic lupus erythematosus by causing synergistic abnormalities in interferon production along with defective clearance of apoptotic cells and over-active B-cell signaling.
人类狼疮与一种基因表达特征密切相关，该特征表现为I型干扰素调节基因的过度表达。尽管有大量证据表明Toll样受体驱动的干扰素产生参与其中，但在标准的狼疮小鼠模型中通常看不到强烈的干扰素特征。相比之下， pristane诱导的狼疮表现出显著的TLR7依赖性干扰素特征。重要的是，人类和小鼠中干扰素产生失调的遗传疾病会导致严重的自身炎症性疾病，但不会导致狼疮的典型表现，这表明干扰素的过度产生不足以导致系统性红斑狼疮本身。小鼠的单基因模型表明，狼疮样疾病可能是由B细胞活化和死细胞清除异常引起的。Pristane可能通过在干扰素产生中引起协同异常，以及凋亡细胞清除缺陷和B细胞信号过度活跃，来模拟人类系统性红斑狼疮。
