EOH Journal Club Seminar - Spring 2017
Date: Thursday February 2, 2017
Time: 11am - 12pm
Presenter: Rahel Birru
Paper: Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency
Authors: Richmond BW, Brucker RM, Han W, Du RH, Zhang Y, Cheng DS, Gleaves L, Abdolrasulnia R, Polosukhina D, Clark PE, Bordenstein SR, Blackwell TS, Polosukhin VV
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 remodeling 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 remodeling. 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 remodeling and emphysema.
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Last Updated On Friday, April 5, 2019 by Borkowski, Matthew Gerard
Created On Friday, January 20, 2017
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