Epithelial glycosylation in gut homeostasis and inflammation

Nat Immunol. 2016 Oct 19;17(11):1244-1251. doi: 10.1038/ni.3587.

Abstract

Intestinal epithelial cells apically express glycans, especially α1,2-fucosyl linkages, which work as a biological interface for the host-microbe interaction. Emerging studies have shown that epithelial α1,2-fucosylation is regulated by microbes and by group 3 innate lymphoid cells (ILC3s). Dysregulation of the gene (FUT2) encoding fucosyltransferase 2, an enzyme governing epithelial α1,2-fucosylation, is associated with various human disorders, including infection and chronic inflammatory diseases. This suggests a critical role for an interaction between microbes, epithelial cells and ILC3s mediated via glycan residues. In this Review, using α1,2-fucose and Fut2 gene expression as an example, we describe how epithelial glycosylation is controlled by immune cells and luminal microbes. We also address the pathophysiological contribution of epithelial α1,2-fucosylation to pathogenic and commensal microbes as well as the potential of α1,2-fucose and its regulatory pathway as previously unexploited targets in the development of new therapeutic approaches for human diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Carbohydrate Metabolism
  • Carbohydrates
  • Fucose / metabolism
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Gastroenteritis / genetics
  • Gastroenteritis / immunology
  • Gastroenteritis / metabolism*
  • Gastroenteritis / microbiology
  • Genetic Predisposition to Disease
  • Glycosylation
  • Homeostasis*
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate
  • Immunity, Mucosal
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Polymorphism, Genetic

Substances

  • Carbohydrates
  • Fucose
  • Fucosyltransferases
  • galactoside 2-alpha-L-fucosyltransferase