Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation

Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both a...

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Autores: Hurtado-Guerrero, Isaac, Hernáez, Bruno, Pinto-Medel, María Jesús, Calonge, Esther, Rodriguez-Bada, José L., Urbaneja, Patricia, Alonso, Ana, Mena-Vázquez, Natalia, Aliaga, Pablo, Issazadeh-Navikas, Shohreh, Pavia, José, Leyva, Laura, Alcamí, José, Alcamí, Antonio, Fernández, Óscar, Oliver-Martos, Begoña
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/209459
Acesso em linha:http://hdl.handle.net/10261/209459
Access Level:acceso abierto
Palavra-chave:Immunology
soluble receptors
IFNAR
interferon
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spelling Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediationHurtado-Guerrero, IsaacHernáez, BrunoPinto-Medel, María JesúsCalonge, EstherRodriguez-Bada, José L.Urbaneja, PatriciaAlonso, AnaMena-Vázquez, NataliaAliaga, PabloIssazadeh-Navikas, ShohrehPavia, JoséLeyva, LauraAlcamí, JoséAlcamí, AntonioFernández, ÓscarOliver-Martos, BegoñaImmunologysoluble receptorsIFNARinterferonSoluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß, but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis. Here we evaluate the potential biological activities of recombinant sIFNAR2 without the mediation of IFN-ß in human cells. Recombinant sIFNAR2 down-regulated the production of IL-17 and IFN-ɣ and reduced the cell proliferation rate. Moreover, it showed a strong antiviral activity, fully protecting the cell monolayer after being infected by the virus. Specific inhibitors completely abrogated the antiviral activity of IFN-ß, but not that of the recombinant sIFNAR2, and there was no activation of the JAK-STAT signaling pathway. Consequently, r-sIFNAR2 exerts immunomodulatory, antiproliferative and antiviral activities without IFN-ß mediation, and could be a promising treatment against viral infections and immune-mediated diseases.This research was funded by grants from the Instituto de Salud Carlos III and co-funded by European Regional Development Fund (ERDF) “A way to build Europe” research project PI13/00927 and Technological Development Project in health DTS/1800045 to B. Oliver-Martos. Also, this work was partially supported by Instituto de Salud Carlos III and co-funded by European Regional Development Fund (ERDF) “A way to build Europe” (projects RD12/0017/0015 and RD16CIII/0002/0001). EMBO Short-TermFellowships (7902) and Estancias formativas de investigación, Junta de Andalucía (EF-0169-2018) to I. Hurtado. JL Rodriguez- Bada issupportedby grants from Red Temática de Investigación Cooperativa: Red Española de Esclerosis Multiple REEM (RD16/0015/0010). Thanks to the collaboration with the Lundbeck Foundation to S.I-N.Peer reviewedMultidisciplinary Digital Publishing InstituteEuropean CommissionInstituto de Salud Carlos IIIJunta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/209459reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/jcm9040959Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2094592026-05-22T06:33:51Z
dc.title.none.fl_str_mv Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
title Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
spellingShingle Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
Hurtado-Guerrero, Isaac
Immunology
soluble receptors
IFNAR
interferon
title_short Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
title_full Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
title_fullStr Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
title_full_unstemmed Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
title_sort Antiviral, immunomodulatory and antiproliferative activities of recombinant soluble IFNAR2 without IFN-ß mediation
dc.creator.none.fl_str_mv Hurtado-Guerrero, Isaac
Hernáez, Bruno
Pinto-Medel, María Jesús
Calonge, Esther
Rodriguez-Bada, José L.
Urbaneja, Patricia
Alonso, Ana
Mena-Vázquez, Natalia
Aliaga, Pablo
Issazadeh-Navikas, Shohreh
Pavia, José
Leyva, Laura
Alcamí, José
Alcamí, Antonio
Fernández, Óscar
Oliver-Martos, Begoña
author Hurtado-Guerrero, Isaac
author_facet Hurtado-Guerrero, Isaac
Hernáez, Bruno
Pinto-Medel, María Jesús
Calonge, Esther
Rodriguez-Bada, José L.
Urbaneja, Patricia
Alonso, Ana
Mena-Vázquez, Natalia
Aliaga, Pablo
Issazadeh-Navikas, Shohreh
Pavia, José
Leyva, Laura
Alcamí, José
Alcamí, Antonio
Fernández, Óscar
Oliver-Martos, Begoña
author_role author
author2 Hernáez, Bruno
Pinto-Medel, María Jesús
Calonge, Esther
Rodriguez-Bada, José L.
Urbaneja, Patricia
Alonso, Ana
Mena-Vázquez, Natalia
Aliaga, Pablo
Issazadeh-Navikas, Shohreh
Pavia, José
Leyva, Laura
Alcamí, José
Alcamí, Antonio
Fernández, Óscar
Oliver-Martos, Begoña
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Instituto de Salud Carlos III
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Immunology
soluble receptors
IFNAR
interferon
topic Immunology
soluble receptors
IFNAR
interferon
description Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß, but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis. Here we evaluate the potential biological activities of recombinant sIFNAR2 without the mediation of IFN-ß in human cells. Recombinant sIFNAR2 down-regulated the production of IL-17 and IFN-ɣ and reduced the cell proliferation rate. Moreover, it showed a strong antiviral activity, fully protecting the cell monolayer after being infected by the virus. Specific inhibitors completely abrogated the antiviral activity of IFN-ß, but not that of the recombinant sIFNAR2, and there was no activation of the JAK-STAT signaling pathway. Consequently, r-sIFNAR2 exerts immunomodulatory, antiproliferative and antiviral activities without IFN-ß mediation, and could be a promising treatment against viral infections and immune-mediated diseases.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/209459
url http://hdl.handle.net/10261/209459
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/jcm9040959
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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