Guarding the frontiers: the biology of type III interferons

Wack, Andreas; Terczyńska-Dyla, Ewa; Hartmann, Rune

doi:10.1038/ni.3212

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Guarding the frontiers: the biology of type III interferons

review-article

Author(s): Andreas Wack ¹ , Ewa Terczyńska-Dyla ² , Rune Hartmann ² ^,

Publication date (Electronic): 21 July 2015

Journal: Nature Immunology

Publisher: Nature Publishing Group US

Keywords: Innate immunity, Inflammation, Interferons, Inflammatory diseases

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Abstract

Type I and III interferons share similar antiviral properties, but there are some important distinctions. Hartmann and colleagues review the specialized functions of type III interferons, including their ability to mediate antiviral functions at barrier surfaces.

Abstract

Type III interferons (IFNs) or IFN-λs regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-λs primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-λs thereby help to maintain healthy mucosal surfaces through immune protection, without the significant immune-related pathogenic risk associated with type I IFN responses. Type III IFNs also target the human liver, with dual effects: they induce an antiviral state in hepatocytes, but specific IFN-λ4 action impairs the clearance of hepatitis C virus and could influence inflammatory responses. This constitutes a paradox that has yet to be resolved.

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Most cited references 93

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IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex.

Sergei V. Kotenko, Grant Gallagher, Vitaliy V Baurin … (2003)

We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO). The expression of IFN-lambda mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2). Both receptor chains are constitutively expressed on a wide variety of human cell lines and tissues and signal through the Jak-STAT (Janus kinases-signal transducers and activators of transcription) pathway. This receptor-ligand system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs.

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Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

Yasuhito Tanaka, Nao Nishida, Masaya Sugiyama … (2009)

The recommended treatment for patients with chronic hepatitis C, pegylated interferon-alpha (PEG-IFN-alpha) plus ribavirin (RBV), does not provide sustained virologic response (SVR) in all patients. We report a genome-wide association study (GWAS) to null virological response (NVR) in the treatment of patients with hepatitis C virus (HCV) genotype 1 within a Japanese population. We found two SNPs near the gene IL28B on chromosome 19 to be strongly associated with NVR (rs12980275, P = 1.93 x 10(-13), and rs8099917, 3.11 x 10(-15)). We replicated these associations in an independent cohort (combined P values, 2.84 x 10(-27) (OR = 17.7; 95% CI = 10.0-31.3) and 2.68 x 10(-32) (OR = 27.1; 95% CI = 14.6-50.3), respectively). Compared to NVR, these SNPs were also associated with SVR (rs12980275, P = 3.99 x 10(-24), and rs8099917, P = 1.11 x 10(-27)). In further fine mapping of the region, seven SNPs (rs8105790, rs11881222, rs8103142, rs28416813, rs4803219, rs8099917 and rs7248668) located in the IL28B region showed the most significant associations (P = 5.52 x 10(-28)-2.68 x 10(-32); OR = 22.3-27.1). Real-time quantitative PCR assays in peripheral blood mononuclear cells showed lower IL28B expression levels in individuals carrying the minor alleles (P = 0.015).

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IL-28, IL-29 and their class II cytokine receptor IL-28R.

Paul Sheppard, Wayne Kindsvogel, Wenfeng Xu … (2003)

Cytokines play a critical role in modulating the innate and adaptive immune systems. Here, we have identified from the human genomic sequence a family of three cytokines, designated interleukin 28A (IL-28A), IL-28B and IL-29, that are distantly related to type I interferons (IFNs) and the IL-10 family. We found that like type I IFNs, IL-28 and IL-29 were induced by viral infection and showed antiviral activity. However, IL-28 and IL-29 interacted with a heterodimeric class II cytokine receptor that consisted of IL-10 receptor beta (IL-10Rbeta) and an orphan class II receptor chain, designated IL-28Ralpha. This newly described cytokine family may serve as an alternative to type I IFNs in providing immunity to viral infection.

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Author and article information

Contributors

Rune Hartmann:

ORCID: http://orcid.org/0000-0003-1159-066X

rh@mbg.au.dk

Journal

Journal ID (nlm-ta): Nat Immunol

Journal ID (iso-abbrev): Nat. Immunol

Title: Nature Immunology

Publisher: Nature Publishing Group US (New York )

ISSN (Print): 1529-2908

ISSN (Electronic): 1529-2916

Publication date (Electronic): 21 July 2015

Publication date (Print): 2015

Volume: 16

Issue: 8

Pages: 802-809

Affiliations

[1 ]GRID grid.451388.3, ISNI 0000 0004 1795 1830, Francis Crick Institute, Mill Hill Laboratory, ; London, United Kingdom

[2 ]GRID grid.7048.b, ISNI 0000 0001 1956 2722, Department of Molecular Biology and Genetics, , Aarhus University, ; Aarhus, Denmark

Author information

Rune Hartmann http://orcid.org/0000-0003-1159-066X

Article

Publisher ID: BFni3212

DOI: 10.1038/ni.3212

PMC ID: 7096991

PubMed ID: 26194286

SO-VID: d329661a-1094-430e-b9ff-7a2a8daf0d7c

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.