IL-13 results in short term epithelial dedifferentation and long term goblet cell expansion in PBECs from patients with asthma

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Introduction: Asthma is a heterogeneous lung disease, characterized by remodeled airways and mucus hypersecretion. Previously, we showed that the airway composition is changed in patients with asthma, showing more mucus-producing cells such as goblet and mucous ciliated cells compared to healthy controls. Within these cells we observed an enrichment for IL-4/IL-13 signaling in asthma. Here, we aim to characterize the short- and long term effects of IL-13 stimulation in primary bronchial epithelial cells (PBECs) from controls and patients with asthma. Methods: Results: At the short term, IL-13 stimulation results in fewer ciliated, deuterosomal and goblet cells. In healthy PBECs, this coincides with an increase of basal resting cells, whereas in asthma an increase in suprabasal cells is observed. At the long term, IL-13 stimulation induced an increase in goblet cells and a decrease in club cells, effects that were both larger in asthma. Conclusion: Five-day IL-13 stimulation of differentiated ALIs results in epithelial cell dedifferentiation after three days in both asthma and control PBECs. The larger increase in goblet cell proportions two weeks after stimulation suggests prolonged effects of IL-13 in asthma PBECs compared to controls. Thus, these results will help to explain the altered airway epithelial composition in patients with asthma.

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