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.
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