Cited by 84Immune Response and InflammationInflammatory Bowel DiseaseGastrointestinal motility and disorders

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

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II, William Alfred Rose, Sakamoto, Kaori, Leifer, Cynthia Anne·2012·Scientific Reports

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.

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Crossref · 10.1038/srep00574

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  • TLR9-/- mice are more susceptible to DSS-induced colitis compared with wild types mice, suggesting that activation of TLR9 is important for protection against intestinal damage through induction of vascular EGF and intestinal progenitor cell differentiation as well as being critical for wound repair mechanisms.

    “TLR9–/– mice are more susceptible to DSS-induced colitis compared with wild types mice, suggesting that activation of TLR9 is important for protection against intestinal damage through induction of vascular EGF and intestinal progenitor cell differentiation as well as being critical for wound repair mechanisms.171”

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Authors
II, W. A. R., Sakamoto, K., & Leifer, C. A.
Affiliations
  • University of Georgia (US)
  • Cornell University (US)
Corresponding author
Leifer, Cynthia Anne
Venue
Scientific Reports
Published
2012-08-14
Volume
2
Issue
1
Pages
574-574
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2010808721
Cited by
84
References
53
Citations by year
2026: 2 · 2025: 8 · 2024: 3 · 2023: 8 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 7 · 2018: 11 · 2017: 3 · 2016: 10 · 2015: 4 · 2014: 6 · 2013: 4
FWCI
1.95
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI076588)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
TLR9, intestinal homeostasis, DSS-induced colitis, intestinal epithelial repair, Hes1, vascular endothelial growth factor, innate immunity, inflammatory bowel disease, host DNA
MeSH terms
Transcription Factor HES-1, Animals, Cell Differentiation, Colon, Female, Intestinal Mucosa, Leukocytes, Stem Cells, Wound Healing, Inflammatory Bowel Diseases, Signal Transduction, Mice, Knockout, Homeodomain Proteins, Genetic Predisposition to Disease, Enterocytes, Vascular Endothelial Growth Factor A, Cell Proliferation, Toll-Like Receptor 9, Mice, Basic Helix-Loop-Helix Proteins

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