Role Of IL-6-IL-27 Complex In Host Antiviral Immune Response

The interleukin(IL)family of cytokines participates in immune response and regulation.We previously found that soluble interleukin-6 receptor(s IL-6R)plays an important role in the host antiviral response.In this study,we detected IL-6-IL-27 complex in serum and throat swab samples from patients infected with influenza A virus.A plasmid expressing the IL-6-IL-27 complex was constructed to explore its biological function.The results indicated that IL-6-IL-27 complex has a stronger antiviral effect than the individual subunits of IL-6,IL-27 A,and EBi3.Furthermore,the activity of the IL-6-IL-27 complex is mainly mediated by the IL-27 A subunit and the receptor IL-27R?.IL-6-IL-27 complex can positively regulate virus-triggered expression of interferon(IFN)and IFN-stimulated genes by interacting with adaptor protein MAVS,potentiating the ubiquitination of TRAF3 and TRAF6,and NF-?B nuclear translocation.The secreted IL-6-IL-27 complex can induce the phosphorylation of STAT1 and STAT3 and shows antiviral activity.Our results demonstrate a previously unrecognized mechanism by which IL-6,IL-27 A,and EBi3 form a large complex both intracellularly and extracellularly,and this complex acts in the host antiviral response.