Mice deficient in intestinal γδ intraepithelial lymphocytes display an altered intestinal O-glycan profile compared with wild-type littermates

Glycobiology. 2015 Jan;25(1):42-54. doi: 10.1093/glycob/cwu088. Epub 2014 Sep 3.

Abstract

Intestinal γδ T-cell receptor-bearing intraepithelial lymphocytes (γδ IELs) play a multifaceted role in maintaining mucosal homeostasis. In order to investigate the relationship between O-glycosylation and inflammation, we carried out an in-depth mass spectrometric comparison of the intestinal O-glycosylation profile of mice lacking γδ IELs (TCRδ(-/-)) and of their wild-type (WT) littermates. A total of 69 nonsulfated and 59 sulfated compositional types of O-glycans were identified in the small intestine and colon of TCRδ(-/-) and WT mice. Our results demonstrated structural differences in intestinal glycosylation in TCRδ(-/-) mice compared with WT littermates. TCRδ(-/-) colons contained a lower proportion of core-2 structures and an increased proportion of core-1 structures whereas TCRδ(-/-) small intestines had a decreased percentage of core-3 structures. The glycan antennae in TCRδ(-/-) colon and small intestine showed altered structural diversity compared with WT mice. There were significant differences in the sialylated species between the TCRδ(-/-) and WT mice with the sialylated Tn antigen found exclusively in the TCRδ(-/-)small intestine, whereas the sulfation pattern remained mostly unchanged. These findings provide novel molecular insights underpinning the role of γδ IELs in maintaining gut homeostasis.

Keywords: MALDI-ToF-MS; O-glycosylation; T-cell receptor-γδ; intestinal intraepithelial T lymphocytes; mouse intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbohydrate Sequence
  • Colon / cytology
  • Colon / immunology
  • Colon / metabolism
  • Female
  • Gene Expression
  • Glycosylation
  • Immunity, Mucosal
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / cytology
  • Intestine, Small / immunology
  • Intestine, Small / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Organ Specificity
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Sialic Acids / chemistry
  • Sialic Acids / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Polysaccharides
  • Receptors, Antigen, T-Cell, gamma-delta
  • Sialic Acids