Griffiths Samantha J, Dunnigan Cory M, Russell Clark D, Haas Jürgen G
Division of Infection and Pathway Medicine, University of Edinburgh Medical School, Edinburgh, UK.
J Innate Immun. 2015;7(3):231-42. doi: 10.1159/000369902. Epub 2015 Jan 23.
Since its discovery in 2003, the type III interferon-λ (IFN-λ) family has been found to contribute significantly to the host response to infection. Whilst IFN-λ shares many features with type I IFN induction and signalling pathways, the tissue-specific restricted expression of its receptor, IL28RA, makes IFN-λ a major mediator of host innate immunity in tissues and organs with a high epithelial cell content. Host susceptibility and responses to infection are known to be heterogeneous, and the identification of common genetic variants linked to disease outcome by genome-wide association studies (GWAS) has underscored the significance of host polymorphisms in responses to infection. Several such GWAS have highlighted the IFN-λ locus on chromosome 19q13 as an area of genetic variation significantly associated with hepatitis C virus (HCV) infection, and the rs12979860 genotype can be used in clinical practice as a biomarker for predicting a successful response to treatment with pegylated IFN and ribavarin. Here, we discuss IFN-λ genetic polymorphisms and their role in HCV and other infectious diseases as well as their potential impact on clinical diagnostics, patient stratification and therapy. Finally, the broader role of IFN-λ in the immunopathogenesis of non-infectious inflammatory diseases is considered.
自2003年被发现以来，III型干扰素-λ（IFN-λ）家族已被发现对宿主的感染反应有重大贡献。虽然IFN-λ在I型干扰素诱导和信号通路方面有许多共同特征，但其受体IL28RA的组织特异性受限表达使IFN-λ成为上皮细胞含量高的组织和器官中宿主固有免疫的主要介质。已知宿主对感染的易感性和反应是异质性的，通过全基因组关联研究（GWAS）鉴定与疾病结局相关的常见基因变异突出了宿主多态性在感染反应中的重要性。几项此类GWAS已强调19号染色体q13上的IFN-λ基因座是与丙型肝炎病毒（HCV）感染显著相关的遗传变异区域，rs12979860基因型可在临床实践中用作预测聚乙二醇化干扰素和利巴韦林治疗成功反应的生物标志物。在此，我们讨论IFN-λ基因多态性及其在HCV和其他传染病中的作用，以及它们对临床诊断、患者分层和治疗的潜在影响。最后，考虑了IFN-λ在非感染性炎症性疾病免疫发病机制中的更广泛作用。
