Boisvert Maude, Shoukry Naglaa H
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) , Montréal, QC , Canada.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada; Département de médecine, Université de Montréal, Montréal, QC, Canada.
Front Immunol. 2016 Dec 23;7:628. doi: 10.3389/fimmu.2016.00628. eCollection 2016.
The interferon (IFN)-λ family of type III cytokines includes the closely related interleukin (IL)-28A (IFN-λ2), IL-28B (IFN-λ3), and IL-29 (IFN-λ1). They signal through the Janus kinases (JAK)-signal transducers and activators of transcription pathway and promote an antiviral state by the induction of expression of several interferon-stimulated genes (ISGs). Contrary to type I IFNs, the effect of IFN-λ cytokines is largely limited to epithelial cells due to the restricted pattern of expression of their specific receptor. Several genome-wide association studies have established a strong correlation between polymorphism in the region of IL-28B gene (encoding for IFN-λ3) and both spontaneous and therapeutic IFN-mediated clearance of hepatitis C virus (HCV) infection, but the mechanism(s) underlying this enhanced viral clearance are not fully understood. IFN-λ3 directly inhibits HCV replication, and studies suggest that polymorphism in the IFN-λ3 and its recently identified overlapping IFN-λ4 govern the pattern of ISGs induced upon HCV infection of hepatocytes. IFN-λ can also be produced by dendritic cells, and apart from its antiviral action on hepatocytes, it can regulate the inflammatory response of monocytes/macrophages, thus acting at the interface between innate and adaptive immunity. Here, we review the current state of knowledge about the role of IFN-λ cytokines in mediating and regulating the immune response during acute and chronic HCV infections.
III型细胞因子干扰素（IFN）-λ家族包括密切相关的白细胞介素（IL）-28A（IFN-λ2）、IL-28B（IFN-λ3）和IL-29（IFN-λ1）。它们通过Janus激酶（JAK）-信号转导子和转录激活因子途径进行信号传导，并通过诱导多种干扰素刺激基因（ISG）的表达来促进抗病毒状态。与I型干扰素不同，由于其特异性受体的表达模式受限，IFN-λ细胞因子的作用主要局限于上皮细胞。多项全基因组关联研究已证实，IL-28B基因（编码IFN-λ3）区域的多态性与丙型肝炎病毒（HCV）感染的自发和治疗性IFN介导清除均密切相关，但这种增强的病毒清除背后的机制尚未完全明确。IFN-λ3直接抑制HCV复制，并且研究表明，IFN-λ3及其最近发现的重叠IFN-λ4中的多态性决定了肝细胞感染HCV后诱导的ISG模式。IFN-λ也可由树突状细胞产生，除了其对肝细胞的抗病毒作用外，它还可调节单核细胞/巨噬细胞的炎症反应，从而在固有免疫和适应性免疫之间发挥作用。在此，我们综述了关于IFN-λ细胞因子在急性和慢性HCV感染期间介导和调节免疫反应作用的当前知识状态。
