title: Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation.
abstract: Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. Interleukin-25 (IL-25) activates type 2-driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we examined whether RV-induced IL-25 could contribute to asthma exacerbations. RV-infected cultured asthmatic bronchial epithelial cells exhibited a heightened intrinsic capacity for IL-25 expression, which correlated with donor atopic status. In vivo human IL-25 expression was greater in asthmatics at baseline and during experimental RV infection. In addition, in mice, RV infection induced IL-25 expression and augmented allergen-induced IL-25. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. Therefore, asthmatic epithelial cells have an increased intrinsic capacity for expression of a pro-type 2 cytokine in response to a viral infection, and IL-25 is a key mediator of RV-induced exacerbations of pulmonary inflammation.
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.
authors.forename: Janine
authors.initials: J
authors.lastname: Beale
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Jayaraman
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.|Imperial College Healthcare National Health Service Trust, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Jackson
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.|Imperial College Healthcare National Health Service Trust, London, UK.
authors.forename: Jonathan D R
authors.initials: JDR
authors.lastname: Macintyre
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.
authors.forename: Ross P
authors.initials: RP
authors.lastname: Walton
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.
authors.forename: Yee
authors.initials: Y
authors.lastname: Man Ching
authors.affiliation: Novartis Institute for Biomedical Research, Horsham, UK.
authors.forename: Betty
authors.initials: B
authors.lastname: Shamji
authors.affiliation: Novartis Institute for Biomedical Research, Horsham, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Novartis Institute for Biomedical Research, Horsham, UK.
authors.forename: John
authors.initials: J
authors.lastname: Westwick
authors.affiliation: MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Division of Asthma, Allergy & Lung Biology, King College London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Cousins
authors.affiliation: MRC Laboratory for Molecular Biology, Cambridge, UK.
authors.forename: You
authors.initials: Y
authors.lastname: Yi Hwang
authors.affiliation: MRC Laboratory for Molecular Biology, Cambridge, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKenzie
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Imperial College Healthcare National Health Service Trust, London, UK.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK.|MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.|Centre for Respiratory Infections, Imperial College London, London, UK.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Bartlett
mesh_terms: D001249:Asthma / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D002478:Cells, Cultured; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D020381:Interleukin-17 / Q000096:biosynthesis*; D010850:Picornaviridae Infections / Q000276:immunology; D011024:Pneumonia, Viral / Q000276:immunology* / Q000821:virology; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors; D012229:Rhinovirus / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17