The intestinal epithelium has to maintain a tight barrier to the harsh luminal environment. The absorptive enterocytes have a polygonal and columnar shape, while mucus-producing goblet cells have a round apical cell shape and a bulky body, raising the question of how epithelial integrity is maintained around these cells. Here, we show that goblet cells induce tight junction fractures between neighboring enterocytes under homeostatic conditions in vivo, which are exacerbated during goblet cell hypertrophy, increasing gut permeability. We demonstrate that these fractures arise from a two-component mechanical interaction: goblet cells push and deform adjacent enterocytes, which rupture depending on tissue rheology controlled by myosin II. These findings reveal that the mechanical interplay between goblet cells and neighboring enterocytes is critical for intestinal epithelial barrier integrity.

Denis Krndija is invited by Katia Ancelin and Julie Chaumeil.