 Epithelial tight junctions, TJs, are the key structures regulating paracellular trafficking of macromolecules. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, which can act as a trigger for the development of intestinal and systemic diseases. This article was authored by Sung Hee Lee.