Maha Zohra Ladjemi1,2, Delphine Gras3, Sébastien Dupasquier1, Bruno Detry1,2, Marylène Lecocq1,4, Céline Garulli3, Chantal Fregimilicka5, Caroline Bouzin5, Sophie Gohy1,4, Pascal Chanez3,6, Charles Pilette1,2,4. 1. 1 Pôle de Pneumologie, ORL, et Dermatologie and. 2. 2 Institute for Walloon Excellence in Lifesciences and Biotechnology, Brussels, Belgium. 3. 3 INSERM U 1067, CNRS UMR 7333, Université Aix-Marseille, Marseille, France. 4. 4 Service de Pneumologie, Cliniques universitaires Saint-Luc, Brussels, Belgium; and. 5. 5 Imaging Platform, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium. 6. 6 Clinique des bronches, de l'allergie et du sommeil, Hôpital Nord, Assistance Publique Hôpitaux de Marseille (APHM), Marseille, France.
Abstract
RATIONALE: Asthma is associated with increased lung IgE production, but whether the secretory IgA system is affected in this disease remains unknown. OBJECTIVES: We explored mucosal IgA transport in human asthma and its potential regulation by T-helper cell type 2 inflammation. METHODS: Bronchial biopsies from asthma and control subjects were assayed for bronchial epithelial polymeric immunoglobulin receptor (pIgR) expression and correlated to T-helper cell type 2 biomarkers. Bronchial epithelium reconstituted in vitro from these subjects, on culture in air-liquid interface, was assayed for pIgR expression and regulation by IL-4/IL-13. MEASUREMENTS AND MAIN RESULTS: Downregulation of pIgR protein was observed in the bronchial epithelium from patients with asthma (P = 0.0002 vs. control subjects). This epithelial defect was not observed ex vivo in the cultured epithelium from patients with asthma. Exogenous IL-13 and IL-4 could inhibit pIgR expression and IgA transcytosis. Mechanistic experiments showed that autocrine transforming growth factor-β mediates the IL-4/IL-13 effect on the pIgR, with a partial contribution of upregulated transforming growth factor-α/epidermal growth factor receptor. CONCLUSIONS: This study shows impaired bronchial epithelial pIgR expression in asthma, presumably affecting secretory IgA-mediated frontline defense as a result of type 2 immune activation of the transforming growth factor pathway.
RATIONALE: Asthma is associated with increased lung IgE production, but whether the secretory IgA system is affected in this disease remains unknown. OBJECTIVES: We explored mucosal IgA transport in humanasthma and its potential regulation by T-helper cell type 2 inflammation. METHODS: Bronchial biopsies from asthma and control subjects were assayed for bronchial epithelial polymeric immunoglobulin receptor (pIgR) expression and correlated to T-helper cell type 2 biomarkers. Bronchial epithelium reconstituted in vitro from these subjects, on culture in air-liquid interface, was assayed for pIgR expression and regulation by IL-4/IL-13. MEASUREMENTS AND MAIN RESULTS: Downregulation of pIgR protein was observed in the bronchial epithelium from patients with asthma (P = 0.0002 vs. control subjects). This epithelial defect was not observed ex vivo in the cultured epithelium from patients with asthma. Exogenous IL-13 and IL-4 could inhibit pIgR expression and IgA transcytosis. Mechanistic experiments showed that autocrine transforming growth factor-β mediates the IL-4/IL-13 effect on the pIgR, with a partial contribution of upregulated transforming growth factor-α/epidermal growth factor receptor. CONCLUSIONS: This study shows impaired bronchial epithelial pIgR expression in asthma, presumably affecting secretory IgA-mediated frontline defense as a result of type 2 immune activation of the transforming growth factor pathway.
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