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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.

Original publication

DOI

10.1038/mi.2016.92

Type

Journal article

Journal

Mucosal Immunol

Publication Date

05/2017

Volume

10

Pages

716 - 726

Keywords

Adoptive Transfer, Animals, Antigens, Dermatophagoides, Cell Movement, Cells, Cultured, Eosinophils, Extracellular Matrix, Female, Hypersensitivity, Interferon Regulatory Factors, Lung, Macrophages, Alveolar, Mice, Mice, Inbred C57BL, Mice, Knockout, Mucus, Pyroglyphidae