The memory of airway epithelium damage in smokers and COPD patients

Carlier, François;Pilette, Charles
(2022) ERS Lung Science Conference 2022 abstracts — Location: Estoril (9.March.2023)

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Background. Chronic obstructive pulmonary disease (COPD) is a devastating lung disease, representing the third cause of mortality worldwide. In COPD, the bronchial epithelium displays several structural and functional abnormalities affecting barrier integrity, cell polarity, and differentiation, as well as epithelial-to-mesenchymal transition (EMT) and inflammation. Although COPD is currently considered an irreversible disease, the (ir)reversible nature of epithelium changes ex vivo remains poorly known. Methods. The persistence of COPD epithelial abnormalities was addressed in very long-term (10 weeks) primary cultures of air/liquid interface (ALI)-reconstituted airway epithelium from non-smoker controls, smoker controls, and COPD patients. The role of inflammation was also explored by stimulating ALI cultures with a cytokine mix consisting of TNF-α, IL-6 and IL-1β. Finally, the cellular niche holding epithelial memory was studied by exploiting a single cell RNA-sequencing database. Results. Almost all epithelial defects (barrier dysfunction, impaired polarity, lineage abnormalities) observed in smokers and COPD patients persisted in vitro up to week 10, except IL-8/CXCL-8 release and EMT which declined over time. Cytokine treatment induced COPD-like changes and reactivated EMT in COPD cells. Progenitor cells of large and small airways, namely basal and club cells, exhibited EMT-related signatures reminiscent of features observed in situ. Conclusions. The airway epithelium from smokers and COPD patients displays a memory of its native state and previous injuries by cigarette smoking, which is multidimensional and sustained for years. This memory probably resides in progenitor cells of the airway epithelium.
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Carlier, F., & Pilette, C. (2022). The memory of airway epithelium damage in smokers and COPD patients. ERJ Open Research, 8(Supp 8), 113. https://doi.org/10.1183/23120541.lsc-2022.113 (Original work published 2022)