Colton Center for Autoimmunity, Department of Medicine, New York University School of Medicine, New York, NY, USA.
Department of Pathology, New York University School of Medicine, New York, NY, USA.
Nat Rev Rheumatol. 2018 Mar 21;14(4):214-228. doi: 10.1038/nrrheum.2018.31.
The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I interferons have a critical role in the defence against viruses, yet in many rheumatic diseases, large subgroups of patients demonstrate persistent activation of the type I interferon pathway. Genetic variations in type I interferon-related genes are risk factors for some rheumatic diseases, and can explain some of the heterogeneity in type I interferon responses seen between patients within a given disease. Inappropriate activation of the immune response via Toll-like receptors and other nucleic acid sensors also contributes to the dysregulation of the type I interferon pathway in a number of rheumatic diseases. Theoretically, differences in type I interferon activity between patients might predict response to immune-based therapies, as has been demonstrated for rheumatoid arthritis. A number of type I interferon and type I interferon pathway blocking therapies are currently in clinical trials, the results of which are promising thus far. This Review provides an overview of the many ways in which the type I interferon system affects rheumatic diseases.
I 型干扰素途径与多种风湿性疾病的发病机制有关，包括系统性红斑狼疮、干燥综合征、肌炎、系统性硬化症和类风湿关节炎。在正常免疫反应中，I 型干扰素在抵抗病毒方面起着至关重要的作用，但在许多风湿性疾病中，大量亚组患者表现出 I 型干扰素途径的持续激活。I 型干扰素相关基因的遗传变异是一些风湿性疾病的危险因素，并且可以解释在给定疾病中患者之间 I 型干扰素反应的异质性。通过 Toll 样受体和其他核酸传感器的免疫反应的不适当激活也导致了许多风湿性疾病中 I 型干扰素途径的失调。理论上，患者之间 I 型干扰素活性的差异可能预测对免疫为基础的治疗的反应，如类风湿关节炎所证明的那样。目前有许多 I 型干扰素和 I 型干扰素途径阻断疗法正在临床试验中，迄今为止，结果是有希望的。这篇综述概述了 I 型干扰素系统影响风湿性疾病的许多方式。
