10.25646/1807Liu, Francesca Diane M.Kenngott, Elisabeth E.Schröter, Micha F.Kühl, AnjaJennrich, SilkeWatzlawick, RalfHoffmann, UteWolff, ThorstenNorley, StephenScheffold, AlexanderStumhofer, Jason S.Saris, Christiaan J. M.Schwab, Jan M.Hunter, Christopher A.Debes, Gudrun F.Hamann, AlfTimed Action of IL-27 Protects from Immunopathology while Preserving Defense in InfluenzaRobert Koch-Institut, Infektionsepidemiologie2014AnimalsCells CulturedChick EmbryoCytoprotection/geneticsCytoprotection/immunologyImmunity Innate/geneticsInfluenza A virus/immunologyInterleukins/physiologyMiceMice Inbred BALB CMice Inbred C57BLMice KnockoutOrthomyxoviridae Infections/geneticsOrthomyxoviridae Infections/immunologyReceptors Cytokine/geneticsRespiratory Tract Infections/immunologyRespiratory Tract Infections/pathologyRespiratory Tract Infections/virologyTime Factors610 MedizinRobert Koch-InstitutRobert Koch-Institut2018-05-072018-05-072014-05-272014-05-08enperiodicalParthttp://edoc.rki.de/oa/articles/rerJraduncFMY/PDF/20G7E8oX904nA.pdfhttp://edoc.rki.de/176904/1882urn:nbn:de:0257-1003670210.1371/journal.ppat.1004110Infection with influenza virus can result in massive pulmonary infiltration and potentially fatal immunopathology. Understanding the endogenous mechanisms that control immunopathology could provide a key to novel adjunct therapies for this disease. Here we show that the cytokine IL-27 plays a crucial role in protection from exaggerated inflammation during influenza virus infection. Using Il-27ra−/− mice, IL-27 was found to limit immunopathology, neutrophil accumulation, and dampened TH1 or TH17 responses via IL-10–dependent and -independent pathways. Accordingly, the absence of IL-27 signals resulted in a more severe disease course and in diminished survival without impacting viral loads. Consistent with the delayed expression of endogenous Il-27p28 during influenza, systemic treatment with recombinant IL-27 starting at the peak of virus load resulted in a major amelioration of lung pathology, strongly reduced leukocyte infiltration and improved survival without affecting viral clearance. In contrast, early application of IL-27 impaired virus clearance and worsened disease. These findings demonstrate the importance of IL-27 for the physiological control of immunopathology and the potential value of well-timed IL-27 application to treat life-threatening inflammation during lung infection.