ArticleAllergy2019
Toll-like receptor 2 stimulation augments esophageal barrier integrity.
Article in Allergy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Causal relationship between eosinophilic esophagitis and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study.Frontiers in immunology · 2024Pooled it
- Proton pump inhibitors modulate esophageal epithelial barrier function and crosstalk with eosinophils.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- A Role for High Mobility Group Box 1 (HMGB1) Release in the Pathogenesis of Gastroesophageal Reflux Disease.Neurogastroenterology and motility · 2025Article
- The role of the esophageal and intestinal microbiome in gastroesophageal reflux disease: past, present, and future.Frontiers in immunology · 2025Review
- Esophageal microbial dysbiosis impairs mucosal barrier integrity via toll-like receptor 2 pathway in patients with gastroesophageal reflux symptoms.Journal of translational medicine · 2024Article
- Development and dysfunction of structural cells in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2024Review
- Interferon-γ signaling in eosinophilic esophagitis has implications for epithelial barrier function and programmed cell death.bioRxiv : the preprint server for biology · 2024Article
- Toll-like receptor signalling via IRAK4 affects epithelial integrity and tightness through regulation of junctional tension.Development (Cambridge, England) · 2023Article
- The immune-epithelial interface in eosinophilic esophagitis: a conversation.Frontiers in allergy · 2023Article
- Eosinophilic Esophagitis beyond Eosinophils - an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023.International archives of allergy and immunology · 2023Review
- Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids.Journal of visualized experiments : JoVE · 2022Article
- Article
- Dysregulation of the epithelial barrier by environmental and other exogenous factors.Contact dermatitis · 2021Review
- Pathophysiology of reflux oesophagitis: role of Toll-like receptors 2 and 4 and Farnesoid X receptor.Virchows Archiv : an international journal of pathology · 2021Article
- Review
- Microbial Colonization and Inflammation as Potential Contributors to the Lack of Therapeutic Success in Oral Squamous Cell Carcinoma.Frontiers in oral health · 2021Review
- Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma.Allergy · 2020Review
- Modeling Epithelial Homeostasis and Reactive Epithelial Changes in Human and Murine Three-Dimensional Esophageal Organoids.Current protocols in stem cell biology · 2020Article
- Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR).The Journal of allergy and clinical immunology · 2020Review
- Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGermline-encoded innate immune pattern recognition receptors (PRR) are expressed at epithelial surfaces and modulate epithelial defenses. Evidence suggests that stimulation of the Toll-like receptor (TLR) family of PRR may regulate epithelial barrier integrity by upregulating tight junction (TJ) complex protein expression, but it is not known whether this mechanism is utilized in esophageal epithelial cells. TJ complex proteins maintain intact barrier function and are dysregulated in atopic disorders including eosinophilic esophagitis.
methodsPattern recognition receptors expression was assessed in EoE and control primary esophageal epithelial cells, demonstrating robust expression of TLR2 and TLR3. The three-dimensional air-liquid interface culture (ALI) model was used to test whether TLR2 or TLR3 stimulation alters epithelial barrier function using an in vitro model of human epithelium. Transepithelial electrical resistance (TEER) and FITC-Dextran permeability were evaluated to assess membrane permeability. ALI cultures were evaluated by histology, immunohistochemistry, Western blotting, and chromatin immunoprecipitation (ChIP).
resultsTLR3 stimulation did not change TEER in the ALI model. TLR2 stimulation increased TEER (1.28- to 1.31-fold) and decreased paracellular permeability to FITC-Dextran, and this effect was abolished by treatment with anti-TLR2 blocking antibody. TJ complex proteins claudin-1 and zonula occludens-1 were upregulated following TLR2 stimulation, and ChIP assay demonstrated altered histone 4 acetyl binding at the TJP1 enhancer and CLDN1 enhancer and promoter following zymosan treatment, implying the occurrence of durable chromatin changes.
conclusionsOur findings implicate the TLR2 pathway as a potential regulator of esophageal epithelial barrier function and suggest that downstream chromatin modifications are associated with this effect.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.