Hurtado-Guerrero Isaac, Hernáez Bruno, Pinto-Medel María J, 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
Instituto de Investigación Biomédica de Málaga-IBIMA, 29009 Málaga, Spain.
UGC Neurociencias. Hospital Regional Universitario de Málaga, 29010 Málaga, Spain.
J Clin Med. 2020 Mar 31;9(4):959. doi: 10.3390/jcm9040959.
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.
细胞因子的可溶性受体能够改变细胞因子的活性，进而影响免疫系统，并且有些可溶性受体在没有细胞因子介导的情况下具有内在生物学活性。可溶性干扰素β（IFN-β）受体是通过IFNAR2的可变剪接产生的，对IFN-β具有激动剂和拮抗剂特性，但其作用尚不清楚。我们之前证明，重组人可溶性IFN-β受体在多发性硬化症小鼠模型中显示出内在治疗效果。在此，我们评估重组sIFNAR2在人细胞中不依赖IFN-β介导的潜在生物学活性。重组sIFNAR2下调了IL-17和IFN-γ的产生，并降低了细胞增殖率。此外，它还表现出强大的抗病毒活性，在病毒感染后能完全保护细胞单层。特异性抑制剂完全消除了IFN-β的抗病毒活性，但对重组sIFNAR2的抗病毒活性没有影响，并且JAK-STAT信号通路未被激活。因此，重组sIFNAR2在没有IFN-β介导的情况下发挥免疫调节、抗增殖和抗病毒活性，可能是治疗病毒感染和免疫介导疾病的一种有前景的方法。
