Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13

• Published in: American journal of respiratory and critical care medicine 2018-06, Vol.197 (11), p.1396-1409
• Main Authors: Ladjemi, Maha Zohra, Gras, Delphine, Dupasquier, Sébastien, Detry, Bruno, Lecocq, Marylène, Garulli, Céline, Fregimilicka, Chantal, Bouzin, Caroline, Gohy, Sophie, Chanez, Pascal, Pilette, Charles
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Allergies; Asthma; Asthma - metabolism; Asthma - physiopathology; Biopsy; Bronchi - metabolism; Chronic obstructive pulmonary disease; Cytokines; Disease; Epidermal growth factor; Female; Gene expression; Humans; Hypotheses; Immunoglobulin A - metabolism; Immunoglobulin A, Secretory - metabolism; Immunoglobulins; Inflammation; Interleukin-4 - metabolism; Kinases; Male; Middle Aged; Mucous membrane; Respiratory Mucosa - metabolism
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201703-0561oc

Asthma is associated with increased lung IgE production, but whether the secretory IgA system is affected in this disease remains unknown. We explored mucosal IgA transport in human asthma and its potential regulation by T-helper cell type 2 inflammation. 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. 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. 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.