Cell Death

The intestinal barrier is established by a single layer of polarized intestinal epithelial cells (IECs) separating bacteria in the intestinal lumen from the immune cells in the lamina propria. IECs in the intestinal crypt form a rapidly proliferating cell population which completely replaces the epithelium with newly generated cells over a period of 4-5 days. Structural integrity in the gut and maintenance of barrier function require that the rates of epithelial cell proliferation and cell death are tightly regulated. Under homeostatic conditions, the dominant mechanism of IEC death is shedding from the villus tip. In the face of injury or starvation other mechanisms of IEC death play larger roles. In response to genotoxic injury as in radiation or chemotherapy, IECs undergo apoptosis. In response to nutrient deprivation, IECs undergo autophagy. Necroptosis can be initiated by TNFα, TLR agonists, ionizing radiation, reactive oxygen species, and other stimuli.