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In contrast, it remains unclear whether ciliated cells are reduced and which pathways dysregulate epithelial differentiation. We hypothesized that bronchial epithelial cell lineage specification is dysregulated in COPD because of an aberrant reprogramming through transforming growth factor (TGF)-\u03b21. Surgical lung tissue from 81 COPD and 61 control (smokers and non-smokers) patients was assessed for bronchial epithelial cell phenotyping by immunohistochemistry, both <jats:italic>in situ<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> in reconstituted air-liquid interface (ALI) cultures. The role of TGF-\u03b21 was studied <jats:italic>in vitro<\/jats:italic>. COPD epithelium in large airways, when compared to controls, showed decreased \u03b2-tubulin IV\u2009+\u2009ciliated cells (4.4%, 2.5\u20138.8% versus 8.5%, 6.3\u201311.8% of surface staining, median and IQR, p\u2009=\u20090.0009) and increased MUC5AC\u2009+\u2009goblet cells (34.8%, 24.4\u201341.9% versus 10.3%, 5.1\u201317.6%, p\u2009&lt;\u20090.0001). Both features were recapitulated in the ALI-cultured epithelium from COPD patients. Exogenous TGF-\u03b21 reduced mucociliary differentiation while neutralizing TGF-\u03b21 during ALI increased both specialized cell types. The COPD airway epithelium displays altered differentiation for ciliated cells, which recapitulates <jats:italic>in vitro<\/jats:italic>, at least in part through TGF-\u03b21.<\/jats:p>","DOI":"10.1038\/s41598-019-54292-x","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T11:03:10Z","timestamp":1575025390000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Altered generation of ciliated cells in chronic obstructive pulmonary disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Sophie","family":"Gohy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois M.","family":"Carlier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Fregimilicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Detry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryl\u00e8ne","family":"Lecocq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha Zohra","family":"Ladjemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn","family":"Verleden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Hoton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Weynand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0694-1947","authenticated-orcid":false,"given":"Caroline","family":"Bouzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Pilette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"54292_CR1","unstructured":"Global Initiative for Chronic Obstructive Lung Disease. 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