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- W2989779838 abstract "Many chronic inflammatory diseases of the respiratory system present with impaired clearance of mucus in the airways, which promotes disease exacerbations and respiratory distress. However, it is incompletely understood why mucociliary clearance is impaired, impeding the development of diagnostic tools and treatment options. Studying these mechanisms in vitro is difficult due to the phenotypic variability and lack of standardized functional assays of mucociliary clearance in cultured tissues. To address this challenge, we developed a novel high-content imaging approach to quantify multiple metrics of ciliary structure and mucus transport function in fully differentiated cultured human in vitro bronchial epithelial cells treated with IL-13, a key mediator of mucociliary dysfunction in allergic asthma. Combining high-speed videomicroscopy with automated signal processing algorithms, we were able to analyze thousands of live tissue recordings and thereby sensitively profile phenotypic changes over time. We discovered that chronic exposure to IL-13 induces gradual loss of tissue-wide ciliary beat polarity in multiciliated epithelial cells, which leads to markedly reduced directional mucus clearance over the course of days to weeks. Our studies suggest that loss of ciliary beat polarity is promoted by IL-13-mediated mislocalization of the planar cell polarity (PCP) protein Celsr1, a known director of cilia orientation. We propose (1) that lL-13-mediated loss of planar cell polarity contributes to impaired mucus clearance in chronically inflamed airways; and (2) that high-content phenotypic profiling can reveal novel airway disease signatures." @default.
- W2989779838 created "2019-12-05" @default.
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- W2989779838 date "2019-09-28" @default.
- W2989779838 modified "2023-09-27" @default.
- W2989779838 title "Late Breaking Abstract - High-content phenotypic profiling reveals that IL-13 impairs planar cell polarity and directional mucus clearance in human airway tissue" @default.
- W2989779838 doi "https://doi.org/10.1183/13993003.congress-2019.oa1898" @default.
- W2989779838 hasPublicationYear "2019" @default.
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