title: IL-27 Limits Type 2 Immunopathology Following Parainfluenza Virus Infection.
abstract: Respiratory paramyxoviruses are important causes of morbidity and mortality, particularly of infants and the elderly. In humans, a T helper (Th)2-biased immune response to these infections is associated with increased disease severity; however, little is known about the endogenous regulators of these responses that may be manipulated to ameliorate pathology. IL-27, a cytokine that regulates Th2 responses, is produced in the lungs during parainfluenza infection, but its role in disease pathogenesis is unknown. To determine whether IL-27 limits the development of pathogenic Th2 responses during paramyxovirus infection, IL-27-deficient or control mice were infected with the murine parainfluenza virus Sendai virus (SeV). Infected IL-27-deficient mice experienced increased weight loss, more severe lung lesions, and decreased survival compared to controls. IL-27 deficiency led to increased pulmonary eosinophils, alternatively activated macrophages (AAMs), and the emergence of Th2 responses. In control mice, IL-27 induced a population of IFN-γ+/IL-10+ CD4+ T cells that was replaced by IFN-γ+/IL-17+ and IFN-γ+/IL-13+ CD4+ T cells in IL-27-deficient mice. CD4+ T cell depletion in IL-27-deficient mice attenuated weight loss and decreased AAMs. Elimination of STAT6 signaling in IL-27-deficient mice reduced Th2 responses and decreased disease severity. These data indicate that endogenous IL-27 limits pathology during parainfluenza virus infection by regulating the quality of CD4+ T cell responses and therefore may have therapeutic potential in paramyxovirus infections.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Gaia
authors.identifier: 0000-0003-1844-9757
authors.initials: G
authors.lastname: Muallem
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Sagie
authors.initials: S
authors.lastname: Wagage
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jonathan H
authors.identifier: 0000-0002-2032-8228
authors.initials: JH
authors.lastname: DeLong
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alex
authors.identifier: 0000-0002-5409-1994
authors.initials: A
authors.lastname: Valenzuela
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Christian
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Harms Pritchard
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Qun
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Buza
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Deepika
authors.initials: D
authors.lastname: Jain
authors.affiliation: Janssen Research & Development, LLC, Immunology Discovery Research, Spring House, Pennsylvania, United States of America.
authors.forename: M Merle
authors.initials: MM
authors.lastname: Elloso
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: López
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology
chemical_list: C486767:Il27 protein, mouse; D007378:Interleukins