Lambda interferons in immunity and autoimmunity

Type I IFNs are well known players in immunity and autoimmunity. They induce potent innate and adaptive immune responses essential for mediating host defenses against viral and bacterial infections but also driving inflammation during chronic inflammatory and autoimmune diseases. Lambda interferons (IFNλs) or type III IFNs, on the other hand, comprise a relatively new family of cytokines sharing homology and functional resemblance with type I IFNs but whose spectrum of activities remains poorly understood. Although IFNλs induce antiviral responses similar to type I IFNs, their restricted pattern of expression suggested that may have more specialized functions at specific body sites such as barrier surfaces. However, recent developments in the field have revealed broader roles of IFNλs in immunity against a diverse range of pathogens including viral, bacterial and fungal infections, and have highlighted unique non-redundant functions of IFNλs that cannot be compensated by type I IFNs. They have also positioned IFNλs as a non-inflammatory or immunoregulatory form of IFNs that possesses the antimicrobial functions of type I IFNs but lacks their pro-inflammatory effects, playing a crucial role in the fine tuning of immune defenses for optimal host protection and minimal host damage. Beyond infections, IFNλs are also emerging as important players in immunity against cancer and autoimmunity, with several studies now demonstrating up-regulation of these molecules at disease sites, and functional involvement in experimental animal models. Here, we critically assess recent advances in our understanding of the IFNλ biology, with emphasis to their emerging roles in cancer and autoimmune diseases, and discuss their potential therapeutic implications.