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Next, PBEC were cultured at the air\u2013liquid interface, and during differentiation for 2\u20133\u2005weeks exposed daily to whole cigarette smoke. Gene expression, protein levels and epithelial cell markers were subsequently assessed. In addition, functional activities and persistence of the cigarette smoke-induced effects upon cessation were determined.<\/jats:p><jats:p>Expression of the polymeric immunoglobulin receptor, secretory leukocyte protease inhibitor and long and short PLUNC (palate, lung and nasal epithelium clone protein) was restricted to luminal cells and exposure of differentiating PBECs to cigarette smoke resulted in a selective reduction of the expression of these luminal cell-restricted respiratory host defence proteins compared to controls. This reduced expression was a consequence of cigarette smoke-impaired end-stage differentiation of epithelial cells, and accompanied by a significant decreased transepithelial transport of IgA and bacterial killing.<\/jats:p><jats:p>These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and patients with chronic obstructive pulmonary disease to respiratory infections.<\/jats:p>","DOI":"10.1183\/13993003.01009-2017","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T13:20:15Z","timestamp":1521120015000},"page":"1701009","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":52,"title":["Aberrant epithelial differentiation by cigarette smoke dysregulates respiratory host defence"],"prefix":"10.1183","volume":"51","author":[{"given":"Gimano 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