TLR9 is important for protection against intestinal damage and for intestinal repair.
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.
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
William Alfred
WA
Rose
Kaori
K
Sakamoto
Cynthia Anne
CA
Leifer
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics* / Q000276:immunology; D000072056:Transcription Factor HES-1; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics* / Q000276:immunology
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051217:Toll-Like Receptor 9; D000072056:Transcription Factor HES-1; D042461:Vascular Endothelial Growth Factor A; C489734:Hes1 protein, mouse