IFN-λ: Unleashing Its Potential in Disease Therapies From Acute Inflammation Regulation to Cancer Immunotherapy

Abstract

Type III interferons (IFN-λ), which include IFN-λ1 (or interleukin [IL]-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) and IFN-λ4, exert their effects through a unique receptor complex composed of interferon lambda receptor 1 (IFNLR1) and IL-10 receptor subunit beta (IL-10R2). Studies have highlighted their critical role in modulating immune response, particularly in the context of autoimmune diseases, viral infections and cancer. Unlike type I IFNs, which are broadly expressed, IFN-λ displays a more tissue-specific expression pattern, predominantly acting on epithelial cells and certain immune cell types, such as neutrophils and B cells. This specificity allows IFN-λ to play a pivotal role in mucosal immunity, particularly at barrier sites, such as the respiratory and gastrointestinal tracts. Emerging evidence suggests that IFN-λ has a dual role in both enhancing antiviral immunity and regulating inflammation, thus offering a promising therapeutic strategy for diseases like systemic lupus erythematosus, rheumatoid arthritis, asthma and various cancers. However, the precise mechanisms by which IFN-λ influence immune modulation and disease progression remain an area of active investigation. This review aims to provide an overview of the structure, function and signalling pathways of IFN-λ, exploring their role in immune-related diseases and discussing potential avenues for therapeutic intervention.