Context Is Key: Delineating the Unique Functions of IFNα and IFNβ in Disease

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jan 7

PMID 33408718

Citations 17

Authors

Lindsey E Fox

Marissa C Locke

Deborah J Lenschow

Affiliations

Soon will be listed here.

Abstract

Type I interferons (IFNs) are critical effector cytokines of the immune system and were originally known for their important role in protecting against viral infections; however, they have more recently been shown to play protective or detrimental roles in many disease states. Type I IFNs consist of IFNα, IFNβ, IFNϵ, IFNκ, IFNω, and a few others, and they all signal through a shared receptor to exert a wide range of biological activities, including antiviral, antiproliferative, proapoptotic, and immunomodulatory effects. Though the individual type I IFN subtypes possess overlapping functions, there is growing appreciation that they also have unique properties. In this review, we summarize some of the mechanisms underlying differential expression of and signaling by type I IFNs, and we discuss examples of differential functions of IFNα and IFNβ in models of infectious disease, cancer, and autoimmunity.

Citing Articles

Feasibility of Using a Type I IFN-Based Non-Animal Approach to Predict Vaccine Efficacy and Safety Profiles.

Abdel-Haq H Vaccines (Basel). 2024; 12(6).

PMID: 38932312 PMC: 11209158. DOI: 10.3390/vaccines12060583.

Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD.

Monk P, Brookes J, Tear V, Batten T, Newall C, Mankowski M Respir Res. 2024; 25(1):228.

PMID: 38811970 PMC: 11138078. DOI: 10.1186/s12931-024-02854-7.

Type I interferon pathway genetic variants in severe COVID-19.

Montenegro A, Clementino M, Yaochite J Virus Res. 2024; 342:199339.

PMID: 38354910 PMC: 10901847. DOI: 10.1016/j.virusres.2024.199339.

Transcriptome Analysis Reveals Anti-Cancer Effects of Isorhapontigenin (ISO) on Highly Invasive Human T24 Bladder Cancer Cells.

Li A, Park S, Li P, Zhou C, Kluz T, Li J Int J Mol Sci. 2024; 25(3).

PMID: 38339062 PMC: 10855786. DOI: 10.3390/ijms25031783.

Endothelial type I interferon response and brain diseases: identifying STING as a therapeutic target.

Duarte N, Shafi A, Penha-Goncalves C, Pais T Front Cell Dev Biol. 2023; 11:1249235.

PMID: 37791071 PMC: 10542901. DOI: 10.3389/fcell.2023.1249235.

References

Crow M . Interferon-alpha: a therapeutic target in systemic lupus erythematosus. Rheum Dis Clin North Am. 2010; 36(1):173-86, x. PMC: 2843146. DOI: 10.1016/j.rdc.2009.12.008. View

Kernbauer E, Maier V, Rauch I, Muller M, Decker T . Route of Infection Determines the Impact of Type I Interferons on Innate Immunity to Listeria monocytogenes. PLoS One. 2013; 8(6):e65007. PMC: 3686784. DOI: 10.1371/journal.pone.0065007. View

Phillips M, Burrows J, Manyando C, Hooft van Huijsduijnen R, Van Voorhis W, Wells T . Malaria. Nat Rev Dis Primers. 2017; 3:17050. DOI: 10.1038/nrdp.2017.50. View

Hardy M, Owczarek C, Jermiin L, Ejdeback M, Hertzog P . Characterization of the type I interferon locus and identification of novel genes. Genomics. 2004; 84(2):331-45. DOI: 10.1016/j.ygeno.2004.03.003. View

Ball E, Sambo M, Martins M, Trovoada M, Benchimol C, Costa J . IFNAR1 controls progression to cerebral malaria in children and CD8+ T cell brain pathology in Plasmodium berghei-infected mice. J Immunol. 2013; 190(10):5118-27. DOI: 10.4049/jimmunol.1300114. View

Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot D, Adam J . Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med. 2014; 20(11):1301-9. DOI: 10.1038/nm.3708. View

Riggs J, Hanna R, Rajan B, Zerrouki K, Karnell J, Sagar D . Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Lupus Sci Med. 2018; 5(1):e000261. PMC: 5890856. DOI: 10.1136/lupus-2018-000261. View

Zhou Y, Li S, Tang Z, Xu C, Huang S, Wu J . Different antiviral effects of IFNα and IFNβ in an HBV mouse model. Immunobiology. 2016; 222(3):562-570. DOI: 10.1016/j.imbio.2016.11.003. View

Yang L, Xue Q, Sun L, Zhu Y, Liu W . Cloning and characterization of a novel feline IFN-omega. J Interferon Cytokine Res. 2007; 27(2):119-27. DOI: 10.1089/jir.2006.0094. View

10.

Daffis S, Samuel M, Suthar M, Keller B, Gale Jr M, Diamond M . Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection. J Virol. 2008; 82(17):8465-75. PMC: 2519659. DOI: 10.1128/JVI.00918-08. View

11.

Krakauer M, Sorensen P, Khademi M, Olsson T, Sellebjerg F . Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-beta treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression. Mult Scler. 2008; 14(5):622-30. DOI: 10.1177/1352458507087136. View

12.

Swann J, Hayakawa Y, Zerafa N, Sheehan K, Scott B, Schreiber R . Type I IFN contributes to NK cell homeostasis, activation, and antitumor function. J Immunol. 2007; 178(12):7540-9. DOI: 10.4049/jimmunol.178.12.7540. View

13.

Amorim Sacramento L, Benevides L, Maruyama S, Tavares L, Fukutani K, Francozo M . TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection. PLoS Pathog. 2020; 16(3):e1008435. PMC: 7135367. DOI: 10.1371/journal.ppat.1008435. View

14.

Heim M . 25 years of interferon-based treatment of chronic hepatitis C: an epoch coming to an end. Nat Rev Immunol. 2013; 13(7):535-42. DOI: 10.1038/nri3463. View

15.

Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S . Multiple sclerosis. Nat Rev Dis Primers. 2018; 4(1):43. DOI: 10.1038/s41572-018-0041-4. View

16.

Gerlach N, Schimmer S, Weiss S, Kalinke U, Dittmer U . Effects of type I interferons on Friend retrovirus infection. J Virol. 2006; 80(7):3438-44. PMC: 1440373. DOI: 10.1128/JVI.80.7.3438-3444.2006. View

17.

Escobar G, Moi D, Ranghetti A, Ozkal-Baydin P, Squadrito M, Kajaste-Rudnitski A . Genetic engineering of hematopoiesis for targeted IFN-α delivery inhibits breast cancer progression. Sci Transl Med. 2014; 6(217):217ra3. DOI: 10.1126/scitranslmed.3006353. View

18.

Reid L, Minato N, GRESSER I, Holland J, KADISH A, Bloom B . Influence of anti-mouse interferon serum on the growth and metastasis of tumor cells persistently infected with virus and of human prostatic tumors in athymic nude mice. Proc Natl Acad Sci U S A. 1981; 78(2):1171-5. PMC: 319969. DOI: 10.1073/pnas.78.2.1171. View

19.

Honda K, Taniguchi T . IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006; 6(9):644-58. DOI: 10.1038/nri1900. View

20.

Morin P, Braganca J, Lin R, Hiscott J, Doly J, Civas A . Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription. J Mol Biol. 2002; 316(5):1009-22. DOI: 10.1006/jmbi.2001.5401. View