IL-13 drives a mucin phenotype: insights from a human apical out airway organoid model

Basal and goblet cell hyperplasia, mucus overproduction, loss of mucociliary clearance, and impaired epithelial regeneration are characteristics of chronic respiratory diseases such as CF and COPD. Here, primary human bronchial epithelial cells were differentiated to apical out organoids in the presence of IL-13 under Matrigel-free conditions. Incubation with IL-13 resulted in loss of organoid motility. Histology, immunohistochemistry and semiquantitative RT-PCR showed that IL-13 induces a basal and goblet cell-predominant phenotype. Loss of cilia was confirmed using proteomic analysis and a lentivirus-based reporter assay. Our data shows that IL-13 induces a switch in differentiation from ciliary organoids to mucus-expressing organoids. Further studies using modern methods such as single-cell RNA sequencing will reveal which pathways along the apical organoids differentiate.