Epithelial cell dysfunction in coeliac disease

Int Rev Cell Mol Biol. 2021:358:133-164. doi: 10.1016/bs.ircmb.2020.09.007. Epub 2020 Oct 28.

Abstract

The intestinal epithelium limits host-luminal interactions and maintains gut homeostasis. Breakdown of the epithelial barrier and villous atrophy are hallmarks of coeliac disease. Besides the well characterized immune-mediated epithelial damage induced in coeliac mucosa, constitutional changes and early gluten direct effects disturb intestinal epithelial cells. The subsequent modifications in key epithelial signaling pathways leads to outnumbered immature epithelial cells that, in turn, facilitate epithelial dysfunction, promote crypt hyperplasia, and increase intestinal permeability. Consequently, underlying immune cells have a greater access to gluten, which boosts the proinflammatory immune response against gluten and positively feedback the epithelial damage loop. Gluten-free diet is an indispensable treatment for coeliac disease patients, but additional therapies are under development, including those that reinforce intestinal epithelial healing. In this chapter, we provide an overview of intestinal epithelial cell disturbances that develop during gluten intake in coeliac disease mucosa.

Keywords: Epigenetics; Gluten-free diet; Gut barrier; Intestinal epithelial cell; Intestinal permeability; Intestinal stem cell; Methylation; Microbiota; Organoid; Wnt signaling.

Publication types

  • Review

MeSH terms

  • Animals
  • Celiac Disease / genetics
  • Celiac Disease / immunology
  • Celiac Disease / pathology*
  • Celiac Disease / physiopathology*
  • Diet
  • Epigenesis, Genetic
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology*
  • Gastrointestinal Microbiome
  • Glutens / adverse effects
  • Humans

Substances

  • Glutens