Reciprocal interactions between commensal bacteria and gamma delta intraepithelial lymphocytes during mucosal injury

J Immunol. 2009 Mar 1;182(5):3047-54. doi: 10.4049/jimmunol.0802705.

Abstract

The intestinal mucosal surface is in direct contact with a vast beneficial microbiota. The symbiotic nature of this relationship is threatened when the surface epithelium is injured, yet little is known about how mucosal surfaces maintain homeostasis with commensal microbes following damage. Gammadelta intraepithelial lymphocytes (gammadelta IEL) reside at the gut epithelial surface, where they stimulate mucosal healing following acute injury. A genome-wide analysis of the gammadelta IEL response to dextran sulfate sodium-induced colonic damage revealed induction of a complex transcriptional program, including coordinate regulation of cytoprotective, immunomodulatory, and antibacterial factors. Studies in germfree mice demonstrated that commensal microbiota regulate key components of this transcriptional program, thus revealing a dialogue between commensal bacteria and gammadelta IEL in injured epithelia. Analysis of TCRdelta-deficient mice indicated that gammadelta T cells are essential for controlling mucosal penetration of commensal bacteria immediately following dextran sulfate sodium-induced damage, suggesting that a key function of gammadelta IEL is to maintain host-microbial homeostasis following acute mucosal injury. Taken together, these findings disclose a reciprocal relationship between gammadelta T cells and intestinal microbiota that promotes beneficial host-microbial relationships in the intestine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / immunology*
  • Colon / drug effects
  • Colon / immunology
  • Colon / microbiology
  • Colon / pathology
  • Dextran Sulfate / toxicity
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Homeostasis / drug effects
  • Homeostasis / immunology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Lymphocyte Subsets / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / genetics

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Dextran Sulfate

Associated data

  • GEO/GSM343263