Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency
Year: 2016
Type: article
Abstract: Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression. Here we show that polymeric immunoglobulin receptor-deficient (pIgR(-/-)) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age. Progressive airway wall remodelling and emphysema in pIgR(-/-) mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase. Re-derivation of pIgR(-/-) mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling. These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema.
Source: Nature Communications
DOI: 10.1038/ncomms11240
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, U.S. Department of Veterans Affairs, American Lung Association, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1245004033, G1475688881, G1678012665, G251251530, G2620099149, G2778465911, G3136118409, G396327662, G402423035, G4043271849, G4175770015, G4412053983, G5027978258, Regulation of Fibrotic Remodeling by the Alveolar Epithelium, G5255697142, G563474107, G5894413795, G6608807841, Building Interdisciplinary Research Careers in Women's Health, G6911627233, G7864029557, G9000002568, G9000009910, G9000016067, G9000019418, G9000039649, G9000043901, G9000074713, G9000089420, G9000124518, G9000196175, G9000300101, Center for Gastrointestinal Biology and Disease, Clinical Utility of a Combined Biomarker Approach to Diagnose Lung Cancer, Interdisciplinary Training Program in Lung Research, Dimensions: The Microbial Basis of Animal Speciation, G949362299
OpenAlex ID: W2319890337