Hypoxia is associated with a decrease of the expression of the polymeric Immunoglobulin Receptor in a model of human respiratory epithelium

• Published in: Revue des maladies respiratoires Vol. 39; no. 2; p. 123
• Main Authors: Gerard, L., Detry, B., Pilette, C.
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.02.2022
• Subjects: Infection-Inflammation; Infection-Inflammation
• ISSN: 0761-8425
• DOI: 10.1016/j.rmr.2022.02.035

Secretion of immunoglobulin A (IgA) constitutes one of the frontline protection of the lung against inhaled pathogens. IgA is actively transported from the basolateral pole up to the apical pole of epithelial cells by the polymeric Immunoglobulin Receptor (pIgR), where a cleavage releases IgA bound to the extracellular part of the receptor called secretory component (SC). Little is known regarding IgA/pIgR regulation in the acute diseased lung. In particular, the regulation of the IgA system by hypoxia remains unexplored. The effects of hypoxia on broncho-epithelial cells were studied in a validated model of human respiratory epithelium reconstituted in vitro upon culture in air/liquid interface (ALI). After full differentiation, the cultured bronchial epithelia were submitted to 1% O2 in an hypoxic chamber for 12 days, upon resting or stimulated (IL-1β, IL-6, TNFα) conditions. In fully ALI-differentiated cultures from 15 control subjects, hypoxia induced a significant decrease of pIgR expression (Western Blot, p=0.0017), SC release in the apical washes (ELISA, 620±797ng/ml vs 4145±4178ng/ml) and pIgR mRNA relative expression (qPCR, p=0.031), irrespectively of inflammatory cytokines. In addition, hypoxia also induced a dedifferentiation as evidenced by cell morphology and epithelial-to-mesenchymal transition (EMT) signatures, including decreased E-cadherin expression (WB, p=0.016). In addition, pharmacological stabilization of HIF-1α recapitulated these features. In a model of reconstituted human airway epithelium, hypoxia alters pIgR expression and cell differentiation, and this probably occurs through the HIF-1α pathway.