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FEBS J. 2016 Jul;283(14):2720-30. doi: 10.1111/febs.13771. Epub 2016 Jun 22.

Death in the intestinal epithelium-basic biology and implications for inflammatory bowel disease.

Blander JM1,2,3,4,5.

Author information

1
Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

Every 4-5 days, intestinal epithelial cells (IEC) are terminated as they reach the end of their life. This process ensures that the epithelium is comprised of the fittest cells that maintain an impermeable barrier to luminal contents and the gut microbiota, as well as the most metabolically able cells that conduct functions in nutrient absorption, digestion, and secretion of antimicrobial peptides. IEC are terminated by apical extrusion-or shedding-from the intestinal epithelial monolayer into the gut lumen. Whether death by apoptosis signals extrusion or death follows expulsion by younger IEC has been a matter of debate. Seemingly a minor detail, IEC death before or after apical extrusion bears weight on the potential contribution of apoptotic IEC to intestinal homeostasis as a consequence of their recognition by intestinal lamina propria phagocytes. In inflammatory bowel disease (IBD), excessive death is observed in the ileal and colonic epithelium. The precise mode of IEC death in IBD is not defined. A highly inflammatory milieu within the intestinal lamina propria, rich in the proinflammatory cytokine, TNF-α, increases IEC shedding and compromises barrier integrity fueling more inflammation. A milestone in the treatment of IBD, anti-TNF-α therapy, may promote mucosal healing by reversing increased and inflammation-associated IEC death. Understanding the biology and consequences of cell death in the intestinal epithelium is critical to the design of new avenues for IBD therapy.

KEYWORDS:

apoptosis; inflammatory bowel disease; intestinal epithelial cell; intestinal tolerance; tumor necrosis factor

PMID:
27250564
PMCID:
PMC4956528
DOI:
10.1111/febs.13771
[Indexed for MEDLINE]
Free PMC Article

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