Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala, Sweden.
Arthritis Res Ther. 2010;12 Suppl 1(Suppl 1):S2. doi: 10.1186/ar2883. Epub 2010 Apr 14.
Type I interferons play an outstanding role in innate and adaptive immunity by enhancing functions of dendritic cells, inducing differentiation of monocytes, promoting immunoglobulin class switching in B cells and stimulating effector functions of T cells. The increased production of IFNα/β by plasmacytoid dendritic cells could be responsible for not only efficient antiviral defence, but it also may be a pathological factor in the development of various autoimmune disorders. The first evidence of a genetic link between type I interferons and autoimmune diseases was the observation that elevated IFNα activity is frequently detected in the sera of patients with systemic lupus erythematosus, and that this trait shows high heritability and familial aggregation in their first-degree healthy relatives. To date, a number of genes involved in interferon signalling have been associated with various autoimmune diseases. Patients with systemic lupus erythematosus, Sjögren's syndrome, dermatomyositis, psoriasis, and a fraction of patients with rheumatoid arthritis display a specific expression pattern of interferon-dependent genes in their leukocytes, termed the interferon signature. Here, in an attempt to understand the role of type I interferons in the pathogenesis of autoimmunity, we review the recent advances in the genetics of autoimmune diseases focusing on the association of genes involved in type I interferon pathways.
I 型干扰素通过增强树突状细胞的功能、诱导单核细胞分化、促进 B 细胞免疫球蛋白类别转换以及刺激 T 细胞效应功能，在先天免疫和适应性免疫中发挥着重要作用。浆细胞样树突状细胞中 IFNα/β 的产生增加不仅可以有效抵抗病毒，而且可能是各种自身免疫性疾病发展的病理因素。I 型干扰素与自身免疫性疾病之间存在遗传联系的第一个证据是观察到系统性红斑狼疮患者的血清中经常检测到 IFNα 活性升高，并且该特征在其一级健康亲属中具有高遗传性和家族聚集性。迄今为止，许多参与干扰素信号转导的基因已与各种自身免疫性疾病相关。系统性红斑狼疮、干燥综合征、皮肌炎、银屑病以及部分类风湿关节炎患者的白细胞中存在干扰素依赖性基因的特定表达模式，称为干扰素特征。在这里，我们试图通过研究自身免疫发病机制中 I 型干扰素的作用，综述自身免疫性疾病遗传学的最新进展，重点关注涉及 I 型干扰素途径的基因的关联。
