{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Critical Care Medicine, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 10, B-1200 Brussels, Belgium",
    "Pôle 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",
    "IREC Imaging Platform (2IP, RRID:SCR_023378), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium",
    "Department of Pathology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium",
    "Department of Pulmonology, CHU-UCL Namur, B-5530 Yvoir, Belgium",
    "Department of Pulmonology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium",
    "Department of Cardiovascular and Thoracic Surgery, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ludovic Gerard",
      "orcid": "0000-0002-8842-6270"
    },
    {
      "affs": [
        1
      ],
      "name": "Marylene Lecocq"
    },
    {
      "affs": [
        1
      ],
      "name": "Bruno Detry"
    },
    {
      "affs": [
        2
      ],
      "name": "Caroline Bouzin",
      "orcid": "0000-0003-0694-1947"
    },
    {
      "affs": [
        3
      ],
      "name": "Delphine Hoton"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "François Carlier",
      "orcid": "0000-0001-6205-0087"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Thomas Plante-Bordeneuve"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Sophie Gohy"
    },
    {
      "affs": [
        6
      ],
      "name": "Valérie Lacroix"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Charles Pilette"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/872mzej7nrx36.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219525",
  "fulltext_url": null,
  "id": "872mzej7nrx36",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9525",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Respiratory Support and Mechanisms"
    ]
  ],
  "openalex": "W7223892641",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/872mzej7nrx36.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219525",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9525"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Respiratory Support and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "Hypoxia Alters Polymeric Immunoglobulin Receptor Expression and Cell Differentiation in the Airway Epithelium",
  "title_text": "Hypoxia Alters Polymeric Immunoglobulin Receptor Expression and Cell Differentiation in the Airway Epithelium",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/872mzej7nrx36",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}