ArticleMucosal immunology2020
TGFβ1 single-nucleotide polymorphism C-509T alters mucosal cell function in pediatric eosinophilic esophagitis.
Article in Mucosal immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Emerging Insights into the Inflammatory Phenotypes of Eosinophilic Esophagitis.Journal of inflammation research · 2026Review
- Genetic Background of Eosinophilic Esophagitis and Esophageal Atresia in Children.Digestive diseases and sciences · 2025Article
- Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction.The Journal of allergy and clinical immunology · 2025Article
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- Development and dysfunction of structural cells in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2024Review
- Minimally Invasive Approaches to Diagnose and Monitor Eosinophilic GI Diseases.Current allergy and asthma reports · 2024Review
- ERBIN and phosphoglucomutase 3 deficiency.Current opinion in immunology · 2023Review
- A Deficiency in the Cytokine TNFSF14/LIGHT Limits Inflammation and Remodeling in Murine Eosinophilic Esophagitis.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Eosinophilic esophagitis: Immune mechanisms and therapeutic targets.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2022Review
- LIGHT controls distinct homeostatic and inflammatory gene expression profiles in esophageal fibroblasts via differential HVEM and LTβR-mediated mechanisms.Mucosal immunology · 2022Article
- A unique esophageal extracellular matrix proteome alters normal fibroblast function in severe eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2021Article
- Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets.Frontiers in physiology · 2021Review
- Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype.Gastroenterology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Eosinophilic esophagitis (EoE) is a chronic Th2 antigen-driven disorder associated with tissue remodeling. Inflammation and remodeling lead to esophageal rigidity, strictures, and dysphagia. TGFβ1 drives esophageal remodeling including epithelial barrier dysfunction and subepithelial fibrosis. A functional SNP in the TGFβ1 gene that increases its transcription (C-509T) is associated with elevated numbers of esophageal TGFβ1-expressing cells. We utilized esophageal biopsies and fibroblasts from TT-genotype EoE children to understand if TGFβ1 influenced fibroblast and epithelial cell function in vivo. Genotype TT EoE esophageal fibroblasts had higher baseline TGFβ1, collagen1α1, periostin, and MMP2 (p < 0.05) gene expression and distinct contractile properties compared with CC genotype (n = 6 subjects per genotype). In vitro TGFβ1 exposure caused greater induction of target gene expression in genotype CC fibroblasts (p < 0.05). Esophageal biopsies from TT-genotype subjects had significantly less epithelial membrane-bound E-cadherin (p < 0.01) and wider cluster distribution at nanometer resolution. TGFβ1 treatment of stratified primary human esophageal epithelial cells and spheroids disrupted transepithelial resistance (p < 0.001) and E-cadherin localization (p < 0.0001). A TGFβ1-receptor-I inhibitor improved TGFβ1-mediated E-cadherin mislocalization. These data suggest that EoE severity can depend on genotypic differences that increase in vivo exposure to TGFβ1. TGFβ1 inhibition may be a useful therapy in subsets of EoE patients.
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