Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.
Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece.
J Autoimmun. 2019 Nov;104:102319. doi: 10.1016/j.jaut.2019.102319. Epub 2019 Aug 31.
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.
I 型干扰素是免疫和自身免疫中的重要角色。它们诱导强烈的先天和适应性免疫反应，对于介导宿主防御病毒和细菌感染至关重要，但也在慢性炎症和自身免疫性疾病中引发炎症。另一方面，λ干扰素（IFNλ）或 III 型干扰素是一组相对较新的细胞因子家族，与 I 型干扰素具有同源性和功能相似性，但它们的作用谱仍知之甚少。尽管 IFNλ 诱导与 I 型干扰素相似的抗病毒反应，但它们的表达模式受限，表明它们可能在特定身体部位（如屏障表面）具有更特殊的功能。然而，该领域的最新进展揭示了 IFNλ 在针对多种病原体（包括病毒、细菌和真菌感染）的免疫中的更广泛作用，并强调了 IFNλ 的独特非冗余功能，无法被 I 型干扰素补偿。它们还将 IFNλ 定位为一种非炎症或免疫调节形式的干扰素，具有 I 型干扰素的抗菌功能，但缺乏其促炎作用，在优化宿主保护和最小化宿主损伤的免疫防御精细调节中发挥关键作用。除了感染，IFNλ 也在癌症和自身免疫中的免疫中崭露头角，有几项研究现在表明这些分子在疾病部位的上调，并在实验动物模型中具有功能参与。在这里，我们批判性地评估了我们对 IFNλ 生物学理解的最新进展，重点是它们在癌症和自身免疫性疾病中的新兴作用，并讨论了它们的潜在治疗意义。
