Cell death at the intestinal epithelial front line

The intestinal epithelium represents the largest epithelial surface in our body. This single‐cell‐layer epithelium mediates important functions in the absorption of nutrients and in the maintenance of barrier function, preventing luminal microorganisms from invading the body. Due to its constant regeneration the intestinal epithelium is a tissue not only with very high proliferation rates but also with very prominent physiological and pathophysiological cell death induction. The normal physiological differentiation and maturation of intestinal epithelial cells leads to their shedding and apoptotic cell death within a few days, without disturbing the epithelial barrier integrity. In contrast excessive intestinal epithelial cell death induced by irradiation, drugs and inflammation severely impairs the vital functions of this tissue. In this review we discuss cell death processes in the intestinal epithelium in health and disease, with special emphasis on cell death triggered by the tumour necrosis factor receptor family. The single cell epithelial layer at the intestinal mucosal surface facilitates nutrient absorption and prevents host invasion by pathogens. The integrity of the epithelial layer is maintained by well‐balanced proliferation and differentiation‐induced death of epithelial cells. Excessive cell death in the intestinal epithelium induced by irradiation, chemicals or inflammatory processes results in devastating conditions for the organism.