Chronopoulou Sofia, Tsochantaridis Ilias
Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Pharmaceuticals (Basel). 2025 May 24;18(6):785. doi: 10.3390/ph18060785.
Type III interferons (IFN-λ) are the most recently identified members of the interferon family, distantly related to type I interferons and members of the interleukin-10 (IL-10). Unlike type I interferons, which have broadly distributed cellular receptors, IFN-λ signals through a heterodimeric receptor complex with primary expression on epithelial cells. This restricted receptor distribution makes IFN-λ a favorable candidate for therapeutic and antiviral applications with reduced side effects. In this review, we describe the molecular structure, signaling mechanisms, and the role of IFN-λ in the innate immunity of epithelial tissue, which are its primary sites of action. Moreover, this review will summarize and critically examine the antiviral potential of IFN-λ based on all published clinical trials conducted for the treatment of COVID-19, and hepatitis B, C and D virus. Furthermore, this review suggests IFN-λ as a promising therapeutic recombinant protein, with special emphasis on its potential for production using alternative expression and advanced drug delivery systems. To emphasize its potential as a therapeutic intervention, the design and engineering of recombinant IFN-λ will be presented, with a focus on its lower side-effect profile compared to Type I interferons.
III型干扰素（IFN-λ）是干扰素家族中最新发现的成员，与I型干扰素和白细胞介素-10（IL-10）成员的亲缘关系较远。与具有广泛分布的细胞受体的I型干扰素不同，IFN-λ通过一种异二聚体受体复合物发出信号，该复合物主要在上皮细胞中表达。这种受限的受体分布使IFN-λ成为具有降低副作用的治疗和抗病毒应用的理想候选者。在本综述中，我们描述了IFN-λ的分子结构、信号传导机制及其在上皮组织固有免疫中的作用，上皮组织是其主要作用部位。此外，本综述将基于所有已发表的用于治疗COVID-19以及乙型、丙型和丁型肝炎病毒的临床试验，总结并批判性地审视IFN-λ的抗病毒潜力。此外，本综述提出IFN-λ是一种有前景的治疗性重组蛋白，特别强调其使用替代表达和先进药物递送系统进行生产的潜力。为强调其作为治疗干预手段的潜力，将介绍重组IFN-λ的设计与工程，重点关注其与I型干扰素相比更低的副作用。
