Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nat Rev Rheumatol. 2021 Jun;17(6):349-362. doi: 10.1038/s41584-021-00606-1. Epub 2021 Apr 27.
Interferons are potent antiviral cytokines that modulate immunity in response to infection or other danger signals. In addition to their antiviral functions, type I interferons (IFNα and IFNβ) are important in the pathogenesis of autoimmune diseases. Type III interferons (IFNλs) were initially described as a specialized system that inhibits viral replication at epithelial barrier surfaces while limiting inflammatory damage. However, evidence now suggests that type III interferons have complex effects on both innate and adaptive immune responses and might also be pathogenic in systemic autoimmune diseases. Concentrations of IFNλs are increased in blood and tissues in a number of autoimmune rheumatic diseases, including systemic lupus erythematosus, and are further associated with specific clinical and laboratory parameters. This Review is aimed at providing a critical evaluation of the current literature on IFNλ biology and how type III interferons might contribute to immune dysregulation and tissue damage in autoimmunity. The potential effects of type III interferons on treatment strategies for autoimmune rheumatic diseases, such as interferon blockade, are also considered.
干扰素是一种有效的抗病毒细胞因子，可调节感染或其他危险信号引起的免疫反应。除了抗病毒功能外，I 型干扰素（IFNα 和 IFNβ）在自身免疫性疾病的发病机制中也很重要。III 型干扰素（IFNλs）最初被描述为一种专门的系统，可在上皮屏障表面抑制病毒复制，同时限制炎症损伤。然而，目前的证据表明，III 型干扰素对先天和适应性免疫反应都有复杂的影响，在系统性自身免疫性疾病中也可能具有致病性。在包括系统性红斑狼疮在内的许多自身免疫性风湿病中，IFNλ 的浓度在血液和组织中增加，并与特定的临床和实验室参数进一步相关。这篇综述旨在对 IFNλ 生物学的现有文献进行批判性评估，并探讨 III 型干扰素如何导致自身免疫中的免疫失调和组织损伤。还考虑了 III 型干扰素对自身免疫性风湿病治疗策略（如干扰素阻断）的潜在影响。
