Dissemin is shutting down on January 1st, 2025

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Public Library of Science, PLoS Pathogens, 5(10), p. e1004110, 2014

DOI: 10.1371/journal.ppat.1004110

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Timed Action of IL-27 Protects from Immunopathology while Preserving Defense in Influenza

Journal article published in 2014 by Francesca Diane M. Liu, Elisabeth E. Kenngott, Micha F. Schröter, Anja Kühl, Silke Jennrich, Ralf Watzlawick, Ute Hoffmann, Thorsten Wolff, Stephen Norley, Alexander Scheffold, Jason S. Stumhofer, Christiaan J. M. Saris, Jan M. Schwab, Christopher A. Hunter, Gudrun F. Debes ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Infection 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.