2. Academic Validation
  3. Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation

Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation

  • J Clin Med. 2020 Mar 31;9(4):959. doi: 10.3390/jcm9040959.
Isaac Hurtado-Guerrero 1 2 3 4,  Bruno Hernáez 5,  María J Pinto-Medel 1 2 3,  Esther Calonge 6,  José L Rodriguez-Bada 1 2 3,  Patricia Urbaneja 1 2 3,  Ana Alonso 1 2 3,  Natalia Mena-Vázquez 1 7,  Pablo Aliaga 1 2,  Shohreh Issazadeh-Navikas 4,  José Pavia 1 8,  Laura Leyva 1 2 3,  José Alcamí 6 9,  Antonio Alcamí 5,  Óscar Fernández 1 8,  Begoña Oliver-Martos 1 2 3
Affiliations

Affiliations

  • 1 Instituto de Investigación Biomédica de Málaga-IBIMA, 29009 Málaga, Spain.
  • 2 UGC Neurociencias. Hospital Regional Universitario de Málaga, 29010 Málaga, Spain.
  • 3 Red Temática de Investigación Cooperativa: Red Española de Esclerosis Múltiple REEM (RD16/0015/0010), 28049 Madrid, Spain.
  • 4 Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, Copenhagen Biocentre, University of Copenhagen, 2200 Copenhagen, Denmark.
  • 5 Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain.
  • 6 AIDS Immunopathology Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda 28220 Madrid, Spain.
  • 7 UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain.
  • 8 Departamento de Farmacología y Pediatría, Facultad de Medicina. Universidad de Málaga, 29010 Málaga, Spain.
  • 9 HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, 08907 Barcelona, Spain.
PMID: 32244308 DOI: 10.3390/jcm9040959
Abstract

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.

Keywords

IFNAR; immunology; interferon; soluble receptors.

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