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The epithelial surfaces of the skin and intestinal, respiratory, and reproductive tracts are persistently exposed to the myriad of microorganisms present in the external environment. Because this constitutes a limited access border, the cells of these epithelia must be able to establish barriers against microbial intruders and to raise the alarm if the barriers are breached. The gastrointestinal epithelium, in particular, forms a critical interface between the internal milieu and the lumen. The barrier formed by the gastrointestinal tract is essential in preventing noxious luminal contents from accessing the interstitial tissues, and must also support digestion and active vectorial transport of nutrients, electrolytes, and water. Therefore, the barrier formed by gastrointestinal epithelium must be highly regulated and selectively permeable.