Integrative genomic analyses on IL28RA, the common receptor of interferon-λ1, -λ2 and -λ3

Abstract

Interferon (IFN)-lambdas, including INF-lambda1, -lambda2, and -lambda3, are a newly described group of cytokines distantly related to the type I IFNs and IL-10 family members. IFN-lambda1, -lambda2, and -lambda3 bind to the same receptor (known as IL28RA) to exert their antiviral, antitumor and immunomodulatory effects. Here, we identified IL28RA genes from the genome of human, chimpanzee, macaque, orangutan, mouse, horse, rat, dog, chicken, and found that only one IL28RA existed in each genome. All the identified IL28RAs are single-pass type I membrane proteins except chicken IL28RA. They belong to the type II cytokine receptor family and contain one fibronectin type-III domain. We found human IL28RA was expressed in lymphs, testes, lymphoma, teratocarcinoma, pediatric pre-B cell acute lymphoblastic leukemia, germinal center B cells, embryonic stem cells, fetal lung, and also expressed in bladder, blood and breast cancers, glioma, head and neck cancer and lung cancer tissues. Three tumor-related transcriptional factor binding sites (AP-2, c-Jun and P53) were identified within the 1.0-kb regions upstream of the transcriptional start site of human IL28RA. Meta-analysis of the prognostic value of IL28RA genes in various cancers found that the expression of IL28RA was indeed related to the cancer prognosis in certain cancers. The STAT1 binding sites in the promoter region of IL28RA implied a specific mechanism for the amplifying effects of IFN-lambdas. The LyF-1 binding sites in the promoter region of IL28RA imply that IFN-lambdas were involved in the differentiation of early B and T cells.