On cell death in the intestinal epithelium and its impact on gut homeostasis

Current Opinion in Gastroenterology
J Magarian Blander

Abstract

Both apoptotic and nonapoptotic cell extrusion preserve the barrier functions of epithelia. Live cell extrusion is the paradigm for homeostatic renewal of intestinal epithelial cells (IEC). By extension, as extruded cells are not apoptotic, this form of cell shedding is thought to be largely ignored by lamina propria phagocytes and without immune consequence. Visualization of apoptotic IEC inside distinct subsets of intestinal phagocytes during homeostasis has highlighted apoptosis as a normal component of the natural turnover of the intestinal epithelium. Analysis of phagocytes with or without apoptotic IEC corpses has shown how apoptotic IEC constrain inflammatory pathways within phagocytes and induce immunosuppressive regulatory CD4 T-cell differentiation. Many of the genes involved overlap with susceptibility genes for inflammatory bowel disease (IBD). Excessive IEC death and loss-of-barrier function is characteristic of IBD. As regulatory and tolerogenic mechanisms are broken in IBD, a molecular understanding of the precise triggers and modes of IEC death as well as their consequences on intestinal inflammation is necessary. This characterization should guide new therapies that restore homeostatic apoptosis, along with its...Continue Reading

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Citations

Mar 10, 2020·The FEBS Journal·Jarvier N MohammedJerry E Chipuk
Jun 5, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ayano IwakiAkihiro Harada
Apr 27, 2020·Apoptosis : an International Journal on Programmed Cell Death·Prashanthi Ramesh, Jan Paul Medema
Jan 28, 2021·International Journal of Molecular Sciences·Shara Francesca RapaStefania Marzocco
Mar 7, 2021·International Journal of Molecular Sciences·Cristiano PagniniBruno Lagana
Apr 4, 2021·International Journal of Environmental Research and Public Health·Pascual-Vicente CrespoFrancisco Maraver
Jun 5, 2021·Free Radical Biology & Medicine·Ji Tae KimB Mark Evers

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis