A critical role for IRF5 in regulating allergic airway inflammation
| Autor: | Clare M. Lloyd, David Saliba, Sara A. Mathie, Miriam Weiss, Adam J. Byrne, Simone A. Walker, Irina A. Udalova, Hayley L. Eames |
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| Přispěvatelé: | Medical Research Council (MRC), Wellcome Trust |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer DISEASE Mice Cell Movement INFECTION Immunology and Allergy ALVEOLAR MACROPHAGES Lung Cells Cultured Mice Knockout biology Pyroglyphidae 11 Medical And Health Sciences respiratory system Adoptive Transfer 3. Good health Extracellular Matrix medicine.anatomical_structure Interferon Regulatory Factors Female Life Sciences & Biomedicine DEFENSE Immunology INNATE Article Proinflammatory cytokine Lung Disorder 03 medical and health sciences Immune system Macrophages Alveolar medicine Hypersensitivity Animals Antigens Dermatophagoides House dust mite Science & Technology business.industry 06 Biological Sciences biology.organism_classification GENE respiratory tract diseases Eosinophils Mice Inbred C57BL Mucus 030104 developmental biology ASTHMA business IRF5 RESPONSES Interferon regulatory factors |
| Zdroj: | Mucosal immunology |
| ISSN: | 1935-3456 1933-0219 |
| Popis: | Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of pro-inflammatory cytokine and responses to infection, however 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 aero-allergen, 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 hyper- responsiveness, mucus secretion and eosinophilic inflammation. Adoptive transfer of IRF5- deficient alveolar macrophages into the WT pulmonary milieu was sufficient to drive airway hyper-reactivity, at baseline or following antigen challenge. These data identify IRF5-expressing macrophages as a key component of the immune defence 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. |
| Databáze: | OpenAIRE |
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