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IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-alpha/beta in IRF1 dependent and independent manners
Nat Commun. 2019 Oct 16;10(1) :4700
PMID: 31619669 PMCID: PMC6795910 URL: https://www.ncbi.nlm.nih.gov/pubmed/31619669
AbstractThe functions of the IL-36 cytokines remain poorly understood. We report a previously unrecognized mechanism whereby IL-36 promotes innate antiviral immunity in mouse and human models of herpes simplex virus-1 (HSV-1) infections. HSV-1 actively suppresses production of type I interferon (IFN); our data reveal that IL-36 overcomes this immune evasion strategy by increasing cellular sensitivity to IFN. IL-36beta deficient mice display impaired IFN responses and poorly restrict viral replication in skin keratinocytes. In mouse and human keratinocytes IL-36 elicits an antiviral state driven by STAT1 and STAT2 via enhanced expression of IFNAR1 and IFNAR2 subunits of the type I IFN receptor. The degree of IFN regulatory factor 1 (IRF1) involvement is species dependent, with IRF1 playing a more prominent role in human cells. Similar mechanisms are activated by IL-1. Overall, IL-36 acts as an antiviral cytokine by potentiating type I IFN signaling and thereby upholds immune responses to viruses that limit the production of IFNs.
Notes2041-1723 Wang, Peng ORCID: http://orcid.org/0000-0001-8695-6721 Gamero, Ana M Jensen, Liselotte E ORCID: http://orcid.org/0000-0002-0267-8312 Journal Article England Nat Commun. 2019 Oct 16;10(1):4700. doi: 10.1038/s41467-019-12318-y.