Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, NY 10021; and Rheumatology Division, Department of Medicine, NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY 10065
J Immunol. 2014 Jun 15;192(12):5459-68. doi: 10.4049/jimmunol.1002795.
Investigations of patients with systemic lupus erythematosus have applied insights from studies of the innate immune response to define IFN-I, with IFN-α as the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I-signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFN-I-induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained antivirus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients.
对系统性红斑狼疮患者的研究应用了固有免疫反应研究的见解，将 IFN-I 确定为这种典型系统性自身免疫疾病发病机制的核心，其中 IFN-α 是主要介质。遗传关联数据确定了核酸降解的调节剂和 TLR 非依赖性、内体 TLR 依赖性以及 IFN-I 信号通路的组成部分，这些都是狼疮疾病易感性的贡献因素。与狼疮血液和组织中 IFN-I 诱导基因转录物的特征基因表达特征一起，这些数据支持这样的结论，即该疾病的许多免疫和病理特征是由 IFN-I 驱动的持续自我导向免疫反应的结果，类似于持续的抗病毒反应。对 IFN-I 和固有免疫反应作用的这一不断扩展的认识表明，候选治疗靶点正在狼疮患者中进行测试。
