Unknown

Dataset Information

0

Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency.


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-?B 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.

SUBMITTER: Richmond BW 

PROVIDER: S-EPMC4822073 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3265275 | BioStudies
2015-01-01 | S-EPMC4451404 | BioStudies
2019-01-01 | S-EPMC6487813 | BioStudies
2015-01-01 | S-EPMC4466573 | BioStudies
2014-01-01 | S-EPMC4198462 | BioStudies
2021-01-01 | S-EPMC7934842 | BioStudies
2019-01-01 | S-EPMC7313423 | BioStudies
2011-01-01 | S-EPMC3074301 | BioStudies
2020-01-01 | S-EPMC7492639 | BioStudies
2012-01-01 | S-EPMC3296457 | BioStudies