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
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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