title: A critical role for IRF5 in regulating allergic airway inflammation.
abstract: Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of proinflammatory cytokine and responses to infection, but its role in regulating pulmonary immune responses to allergen is unknown. We used genetic ablation, adenoviral vector-driven overexpression, and adoptive transfer approaches to interrogate the role of IRF5 in pulmonary immunity and during challenge with the aeroallergen, house dust mite. Global IRF5 deficiency resulted in impaired lung function and extracellular matrix (ECM) deposition. IRF5 was also essential for effective responses to inhaled allergen, controlling airway hyperresponsiveness, mucus secretion, and eosinophilic inflammation. Adoptive transfer of IRF5-deficient alveolar macrophages into the wild-type pulmonary milieu was sufficient to drive airway hyperreactivity, at baseline or following antigen challenge. These data identify IRF5-expressing macrophages as a key component of the immune defense of the airways. Manipulation of IRF5 activity in the lung could therefore be a viable strategy for the redirection of pulmonary immune responses and, thus, the treatment of lung disorders.
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.|Inflammation, Repair & Development Section, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Byrne
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Inflammation, Repair & Development Section, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Mathie
authors.affiliation: Inflammation, Repair & Development Section, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Walker
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: H L
authors.initials: HL
authors.lastname: Eames
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Saliba
authors.affiliation: Inflammation, Repair & Development Section, National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Lloyd
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
authors.forename: I A
authors.initials: IA
authors.lastname: Udalova
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D050835:Interferon Regulatory Factors; C498178:Irf5 protein, mouse