TLR9 is important for protection against intestinal damage and for intestinal repair

Sci Rep. 2012;2:574. doi: 10.1038/srep00574. Epub 2012 Aug 14.

Abstract

Toll-like receptors (TLRs) are innate receptors critical for host defense, and play a role in normal biological processes. For example, host DNA, a TLR9 ligand, stimulates epithelial repair following skin wounding. TLR signaling also plays a crucial role in regulating intestinal homeostasis. We therefore asked whether TLR9 is important for intestinal wound repair using a dextran sulfate sodium (DSS)-induced intestinal damage and repair model. We showed that TLR9-deficient mice are more susceptible to DSS, and exhibited delayed wound repair at both the clinical and histologic levels. TLR9-deficient mice showed reduced gene expression of hairy enhancer of split 1, an intestinal progenitor cell differentiation factor, and vascular endothelial growth factor, a growth factor important for epithelial cell restitution. Therefore, we conclude that TLR stimulation may play a normal role in regulating intestinal homeostasis and could potentially be a novel therapeutic target to enhance intestinal wound repair in inflammatory bowel diseases.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Colon / metabolism
  • Colon / pathology
  • Enterocytes / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology*
  • Leukocytes / immunology
  • Leukocytes / pathology
  • Mice
  • Mice, Knockout
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Toll-Like Receptor 9 / genetics*
  • Toll-Like Receptor 9 / immunology
  • Transcription Factor HES-1
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / genetics*
  • Wound Healing / immunology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Toll-Like Receptor 9
  • Transcription Factor HES-1
  • Vascular Endothelial Growth Factor A