Hypoxia Alters Polymeric Immunoglobulin Receptor Expression and Cell Differentiation in the Airway Epithelium
7 affiliations
- 1Department of Critical Care Medicine, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, B-1200 Brussels, Belgium
- 2Pôle de Pneumologie, O.R.L. et Dermatologie (LuNS, Lung-Nose-Skin), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium
- 3IREC Imaging Platform (2IP, RRID:SCR_023378), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium
- 4Department of Pathology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium
- 5Department of Pulmonology, CHU-UCL Namur, B-5530 Yvoir, Belgium
- 6Department of Pulmonology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium
- 7Department of Cardiovascular and Thoracic Surgery, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium
Abstract
Secretion of immunoglobulin A (IgA), actively transported across the airway epithelium (AE) by the polymeric immunoglobulin receptor (pIgR), represents a key defense of the lung against pathogens. Dysregulation of the IgA/pIgR system has been reported in respiratory diseases, but the underlying mechanism, and particularly the effects of hypoxia, remains poorly characterized. The effects of hypoxia were investigated using the model of human AE reconstituted in vitro upon culture in the air/liquid interface (ALI). AE was exposed to 1% O2, upon resting or inflammatory conditions. Mechanistic studies included pharmacological stabilization of HIF-1α and inhibition of TGF-β signaling. Additionally, HIF-1α and TGF-β pathways were analyzed by multiplex fluorescence immunostaining of lung tissue from patients with acute respiratory distress syndrome (ARDS) and controls. In ALI AE cultures from 22 subjects, hypoxia significantly reduced pIgR expression (mRNA and proteic), regardless of inflammation. Hypoxia also altered AE structure and cell differentiation, leading to a loss of ciliated and goblet cells. Both hypoxia and pharmacological stabilization of HIF-1α recapitulated these effects and induced increased TGF-β2 expression. In lung tissue from ARDS patients, the AE exhibited reduced pIgR expression, associated with increased HIF-1α stabilization and TGF-β2 expression. Hypoxia induced pIgR downregulation and impaired cell differentiation, through HIF-1α stabilization and subsequent autocrine TGF-β2 signaling, providing a novel pathway underlying altered lung IgA immunity in disease.
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BibTeX
@article{gerard2026hypoxia,
title = {{Hypoxia Alters Polymeric Immunoglobulin Receptor Expression and Cell Differentiation in the Airway Epithelium}},
author = {Ludovic Gerard and Marylene Lecocq and Bruno Detry and Caroline Bouzin and Delphine Hoton and François Carlier and Thomas Plante-Bordeneuve and Sophie Gohy and Valérie Lacroix and Charles Pilette},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219525},
url = {https://www.mdpi.com/1422-0067/27/21/9525},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hypoxia Alters Polymeric Immunoglobulin Receptor Expression and Cell Differentiation in the Airway Epithelium
AU - Ludovic Gerard
AU - Marylene Lecocq
AU - Bruno Detry
AU - Caroline Bouzin
AU - Delphine Hoton
AU - François Carlier
AU - Thomas Plante-Bordeneuve
AU - Sophie Gohy
AU - Valérie Lacroix
AU - Charles Pilette
PY - 2026
DA - 2026/10/24
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219525
UR - https://www.mdpi.com/1422-0067/27/21/9525
AB - Secretion of immunoglobulin A (IgA), actively transported across the airway epithelium (AE) by the polymeric immunoglobulin receptor (pIgR), represents a key defense of the lung against pathogens. Dysregulation of the IgA/pIgR system has been reported in respiratory diseases, but the underlying mechanism, and particularly the effects of hypoxia, remains poorly characterized. The effects of hypoxia were investigated using the model of human AE reconstituted in vitro upon culture in the air/liquid interface (ALI). AE was exposed to 1% O2, upon resting or inflammatory conditions. Mechanistic studies included pharmacological stabilization of HIF-1α and inhibition of TGF-β signaling. Additionally, HIF-1α and TGF-β pathways were analyzed by multiplex fluorescence immunostaining of lung tissue from patients with acute respiratory distress syndrome (ARDS) and controls. In ALI AE cultures from 22 subjects, hypoxia significantly reduced pIgR expression (mRNA and proteic), regardless of inflammation. Hypoxia also altered AE structure and cell differentiation, leading to a loss of ciliated and goblet cells. Both hypoxia and pharmacological stabilization of HIF-1α recapitulated these effects and induced increased TGF-β2 expression. In lung tissue from ARDS patients, the AE exhibited reduced pIgR expression, associated with increased HIF-1α stabilization and TGF-β2 expression. Hypoxia induced pIgR downregulation and impaired cell differentiation, through HIF-1α stabilization and subsequent autocrine TGF-β2 signaling, providing a novel pathway underlying altered lung IgA immunity in disease.
SN - 1422-0067
ER -