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

J. Magarian Blander

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations

Abstract

Purpose of reviewBoth 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.Recent findingsVisualization 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).SummaryExcessive 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 associated programs of immune tolerance and immunosuppression, to achieve mucosal healing and long-term remission.

Original languageEnglish
Pages (from-to)413-419
Number of pages7
JournalCurrent Opinion in Gastroenterology
Volume34
Issue number6
DOIs
StatePublished - 1 Nov 2018
Externally publishedYes

Keywords

  • TNF-α
  • cell death
  • inflammatory bowel disease
  • intestinal epithelium
  • intestinal mononuclear phagocyte

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