ArticleThe Journal of biological chemistry2018
Defining the distinct, intrinsic properties of the novel type I interferon, IFNϵ.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Age-dependent expression and antiviral activity of interferon epsilon in respiratory epithelium.Journal of virology · 2026Article
- Article
- The Dual Role of Interferon Signaling in Myeloproliferative Neoplasms: Pathogenesis and Targeted Therapeutics.Cancers · 2025Review
- Decidual Cells Induce Release of Free and Exosome-Bound Interferon Epsilon From Vaginal Epithelial Cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Article
- Interferon Epsilon: Properties and Functions.Current molecular medicine · 2025Review
- The complexity of immune evasion mechanisms throughout the metastatic cascade.Nature immunology · 2024Review
- Structural and Functional Characterization of a Fish Type I Subgroup d IFN Reveals Its Binding to Receptors.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Interferon-epsilon is a novel regulator of NK cell responses in the uterus.EMBO molecular medicine · 2024Article
- Structure-function of type I and III interferons.Current opinion in immunology · 2024Review
- Expression of Interferon Epsilon in Mucosal Epithelium is Regulated by Elf3.Molecular and cellular biology · 2024Article
- Upregulation of IFNE in cervical biopsies of patients with high-risk human papillomavirus infections.Immunity, inflammation and disease · 2023Article
- Article
- Functional interferon-epsilon gene polymorphisms and sexually transmitted infections of the endometrium.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Article
- Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.PLoS pathogens · 2023Article
- The Analyses of Cetacean Virus-Responsive Genes Reveal Evolutionary Marks in Mucosal Immunity-Associated Genes.Biochemical genetics · 2022Article
- Spatiotemporal regulation of human IFN-ε and innate immunity in the female reproductive tract.JCI insight · 2022Article
- Interferon Epsilon Signaling Confers Attenuated Zika Replication in Human Vaginal Epithelial Cells.Pathogens (Basel, Switzerland) · 2022Article
- Article
- Isolation and characterization of the mink interferon-epsilon gene and its antiviral activity.Frontiers in veterinary science · 2022Article
- Structural and Functional Analyses of Type I IFNa Shed Light Into Its Interaction With Multiple Receptors in Fish.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The type I interferons (IFNs) are a family of cytokines with diverse biological activities, including antiviral, antiproliferative, and immunoregulatory functions. The discovery of the hormonally regulated, constitutively expressed IFNϵ has suggested a function for IFNs in reproductive tract homeostasis and protection from infections, but its intrinsic activities are untested. We report here the expression, purification, and functional characterization of murine IFNϵ (mIFNϵ). Recombinant mIFNϵ (rmIFNϵ) exhibited an α-helical fold characteristic of type I IFNs and bound to IFNα/β receptor 1 (IFNAR1) and IFNAR2, but, unusually, it had a preference for IFNAR1. Nevertheless, rmIFNϵ induced typical type I IFN signaling activity, including STAT1 phosphorylation and activation of canonical type I IFN signaling reporters, demonstrating that it uses the JAK-STAT signaling pathway. We also found that rmIFNϵ induces the activation of T, B, and NK cells and exhibits antiviral, antiproliferative, and antibacterial activities typical of type I IFNs, albeit with 100-1000-fold reduced potency compared with rmIFNα1 and rmIFNβ. Surprisingly, although the type I IFNs generally do not display cross-species activities, rmIFNϵ exhibited high antiviral activity on human cells, suppressing HIV replication and inducing the expression of known HIV restriction factors in human lymphocytes. Our findings define the intrinsic properties of murine IFNϵ, indicating that it distinctly interacts with IFNAR and elicits pathogen-suppressing activity with a potency enabling host defense but with limited toxicity, appropriate for a protein expressed constitutively in a sensitive mucosal site, such as the reproductive tract.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.