Polymeric immunoglobulin receptor expression is downregulated in severe COPD: role of TGF-1
(2013) Munich lung conference — Location: Munich (2013)
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- POLYMERIC IMMUNOGLOBULIN RECEPTOR EXPRESSION IS DOWNREGULATED IN SEVERE COPD: ROLE OF TGF-1 Gohy S, Detry B, Bouzin C, Weynand B, Lecocq M, Sibille Y and Pilette C. Objectives The generation of protective secretory IgA relies on the epithelial polymeric immunoglobulin receptor (pIgR). pIgR expression is reduced in COPD, but correlation to disease severity and underlying mechanisms remain unknown. Materials and methods Surgical lung tissue and primary bronchial epithelium (cultured in air-liquid interface, ALI) obtained from a large series of patients (n=55) undergoing lung surgery for a solitary tumor were studied for pIgR expression (by immunochemistry, RT-qPCR and Elisa) and for IgA transcytosis. Statistics included non-parametric Mann-Whitney U test, following Kruskal-Wallis test for multiple comparisons, and Spearman’s correlation test. Results pIgR immunostaining was decreased in the bronchial epithelium from severe COPD (p=0.04, 1 to 15% of positive area) compared to controls (5 to 26% of positive area), while pIgR transcription was upregulated in smokers and mild-to-moderate COPD compared to controls (p=0.008 and p<0.0001 respectively). In ALI conditions, the release of free secretory component (SC) was strongly induced ( 50 fold increase, as compared to submerged cultures) and pIgR expression increased progressively from 1 to 5 weeks of culture. pIgR immunostaining was decreased in ALI-HBEC from moderate COPD patients (p=0.04, 10 to 25 of positive area) compared to controls (12 to 37% of positive area). In addition, the IgA-transcytosis capacity was decreased in COPD ALI-HBEC as compared to control smokers and mild COPD. COPD cultures released more TGF-1, reflecting increased epithelial immunostaining in COPD lung tissue. Finally, exogenous TGF-1 was able to dose-dependently inhibit pIgR transcription and IgA transcytosis, in parallel to induction of EMT. Conclusion pIgR downregulation in COPD is correlated to disease severity, and the bronchial epithelium reconstituted in vitro from these patients retains its aberrant imprinting for pIgR expression. This study also links pIgR downregulation to TGF--driven (re)programming of the bronchial epithelium, which results in impaired secretory IgA immunity in patients with severe COPD.
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Gohy, S., Detry, B., Bouzin, C., Weynand, B., Lecocq, M., Sibille, Y., & Pilette, C. (2013). Polymeric immunoglobulin receptor expression is downregulated in severe COPD: role of TGF-1. Munich lung conference, Munich. https://hdl.handle.net/2078.5/200137