Search

Your search keyword '"Kurten, Richard C."' showing total 7 results
Start Over Author "Kurten, Richard C." Topic esophagus
7 results on '"Kurten, Richard C."'

1. Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype.

Author

Manresa MC, Chiang AWT, Kurten RC, Dohil R, Brickner H, Dohil L, Herro R, Akuthota P, Lewis NE, Croft M, and Aceves SS

Subjects
Adolescent, Case-Control Studies, Cells, Cultured, Child, Child, Preschool, Eosinophilic Esophagitis immunology, Eosinophilic Esophagitis pathology, Esophagus immunology, Esophagus pathology, Female, Fibroblasts immunology, Fibroblasts pathology, Humans, Intercellular Adhesion Molecule-1 metabolism, Male, Phenotype, Receptors, Tumor Necrosis Factor, Member 14 metabolism, Signal Transduction, T-Lymphocytes immunology, Tumor Necrosis Factor Ligand Superfamily Member 14 genetics, Up-Regulation, Cell Differentiation, Eosinophilic Esophagitis metabolism, Esophagus metabolism, Fibroblasts metabolism, Inflammation Mediators metabolism, Paracrine Communication, T-Lymphocytes metabolism, Tumor Necrosis Factor Ligand Superfamily Member 14 metabolism
Abstract

Background & Aims: Eosinophilic esophagitis (EoE) is an antigen-mediated eosinophilic disease of the esophagus that involves fibroblast activation and progression to fibrostenosis. Cytokines produced by T-helper type 2 cells and transforming growth factor beta 1 (TGFβ1) contribute to the development of EoE, but other cytokines involved in pathogenesis are unknown. We investigate the effects of tumor necrosis factor superfamily member 14 (TNFSF14, also called LIGHT) on fibroblasts in EoE., Methods: We analyzed publicly available esophageal CD3 + T-cell single-cell sequencing data for expression of LIGHT. Esophageal tissues were obtained from pediatric patients with EoE or control individuals and analyzed by immunostaining. Human primary esophageal fibroblasts were isolated from esophageal biopsy samples of healthy donors or patients with active EoE. Fibroblasts were cultured; incubated with TGFβ1 and/or LIGHT; and analyzed by RNA sequencing, flow cytometry, immunoblots, immunofluorescence, or reverse transcription polymerase chain reaction. Eosinophils were purified from peripheral blood of healthy donors, incubated with interleukin 5, cocultured with fibroblasts, and analyzed by immunohistochemistry., Results: LIGHT was up-regulated in the esophageal tissues from patients with EoE, compared with control individuals, and expressed by several T-cell populations, including T-helper type 2 cells. TNF receptor superfamily member 14 (TNFRSF14, also called HVEM) and lymphotoxin beta receptor are receptors for LIGHT that were expressed by fibroblasts from healthy donors or patients with active EoE. Stimulation of esophageal fibroblasts with LIGHT induced inflammatory gene transcription, whereas stimulation with TGFβ1 induced transcription of genes associated with a myofibroblast phenotype. Stimulation of fibroblasts with TGFβ1 increased expression of HVEM; subsequent stimulation with LIGHT resulted in their differentiation into cells that express markers of myofibroblasts and inflammatory chemokines and cytokines. Eosinophils tethered to esophageal fibroblasts after LIGHT stimulation via intercellular adhesion molecule-1., Conclusions: T cells in esophageal tissues from patients with EoE express increased levels of LIGHT compared with control individuals, which induces differentiation of fibroblasts into cells with inflammatory characteristics. TGFβ1 increases fibroblast expression of HVEM, a receptor for LIGHT. LIGHT mediates interactions between esophageal fibroblasts and eosinophils via ICAM1. This pathway might be targeted for the treatment of EoE., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2020
Full Text
View/download PDF

2. Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis.

Author

Doshi A, Khamishon R, Rawson R, Duong L, Dohil L, Myers SJ, Bell B, Dohil R, Newbury RO, Barrett KE, Kurten RC, and Aceves SS

Subjects
Biopsy, Child, Eosinophilic Esophagitis pathology, Epithelial Cells metabolism, Epithelium metabolism, Epithelium pathology, Esophagus pathology, Female, Humans, Male, Antigens, CD metabolism, Cadherins metabolism, Eosinophilic Esophagitis metabolism, Esophagus metabolism, Interleukin-9 metabolism, Receptors, Interleukin-9 metabolism
Abstract

Background: Eosinophilic esophagitis (EoE) is a chronic TH2-assocated inflammatory condition accompanied by substantial impairments in epithelial barrier function and increased numbers of interleukin 9 (IL-9) expressing inflammatory cells. While IL-9 is known to affect barrier function in the intestine, the functional effects of IL-9 on the esophagus are unclear. Herein we aimed to understand the expression of the IL-9 receptor and effects of IL-9 on the epithelium in EoE., Methods: We used esophageal biopsies from pediatric EoE patients with active and inactive disease to analyze the expression of the IL-9 receptor, the adherens junction protein E-cadherin and the tight junction protein claudin-1. We treated primary human esophageal epithelial cells with IL-9 to understand its effects on E-cadherin expression and function., Results: Active EoE subjects had increased epithelial expression of IL-9 receptor mRNA and protein (P < 0.05) and decreased membrane bound E-cadherin (P < 0.01) and claudin-1 (P < 0.05) expression. IL-9 receptor expression and mislocalized claudin-1 positively correlated and while membrane bound E-cadherin expression negatively correlated with the degree of histologic epithelial remodeling (P < 0.05). IL-9 decreased epithelial resistance in stratified primary human esophageal epithelial cells (P < 0.01) and membrane bound E-cadherin in epithelial cell monolayers (P < 0.01)., Conclusions: These data suggest that IL-9, its receptor, and its effects on E-cadherin may be important mechanisms for epithelial barrier disruption in EoE.

Published
2019
Full Text
View/download PDF

3. Rigid substrate induces esophageal smooth muscle hypertrophy and eosinophilic esophagitis fibrotic gene expression.

Author

Tkachenko E, Rawson R, La E, Doherty TA, Baum R, Cavagnero K, Miyanohara A, Dohil R, Kurten RC, and Aceves SS

Subjects
Eosinophilic Esophagitis genetics, Fibrosis, Gene Expression, Genetic Markers, Humans, Hypertrophy, Up-Regulation, Calcium-Binding Proteins genetics, Eosinophilic Esophagitis pathology, Esophagus pathology, Muscle, Smooth pathology
Published
2016
Full Text
View/download PDF

4. Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis.

Author

Doherty TA, Baum R, Newbury RO, Yang T, Dohil R, Aquino M, Doshi A, Walford HH, Kurten RC, Broide DH, and Aceves S

Subjects
Adolescent, Antigens, CD genetics, Antigens, CD immunology, Biopsy, Child, Child, Preschool, Cytokines pharmacology, Eosinophilic Esophagitis genetics, Eosinophilic Esophagitis pathology, Eosinophils pathology, Esophagus pathology, Female, Gene Expression Regulation, Humans, Immunity, Innate, Immunophenotyping, Infant, Interleukin-13 genetics, Interleukin-13 immunology, Interleukin-33 pharmacology, Interleukin-5 genetics, Interleukin-5 immunology, Lymphocyte Count, Lymphocyte Subsets drug effects, Lymphocyte Subsets pathology, Primary Cell Culture, Receptors, Immunologic genetics, Receptors, Immunologic immunology, Receptors, Prostaglandin genetics, Receptors, Prostaglandin immunology, Signal Transduction, Thymic Stromal Lymphopoietin, Cytokines immunology, Eosinophilic Esophagitis immunology, Eosinophils immunology, Esophagus immunology, Interleukin-33 immunology, Lymphocyte Subsets immunology
Published
2015
Full Text
View/download PDF

5. Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype

Author

Manresa, Mario C, Chiang, Austin WT, Kurten, Richard C, Dohil, Ranjan, Brickner, Howard, Dohil, Lucas, Herro, Rana, Akuthota, Praveen, Lewis, Nathan E, Croft, Michael, and Aceves, Seema S

Subjects
Male, Tumor Necrosis Factor Ligand Superfamily Member 14, Adolescent, T-Lymphocytes, Cells, Member 14, Clinical Sciences, Food Allergies, ICAM1, Immune Regulation, Paediatrics and Reproductive Medicine, Esophagus, Clinical Research, Paracrine Communication, Receptors, Eosinophilia, Genetics, Humans, 2.1 Biological and endogenous factors, Aetiology, Child, Preschool, Cultured, Gastroenterology & Hepatology, Inflammatory and immune system, Neurosciences, Cell Differentiation, Eosinophilic Esophagitis, Fibroblasts, Intercellular Adhesion Molecule-1, Fibrosis, Up-Regulation, Fibrogenesis, Phenotype, Case-Control Studies, Female, Inflammation Mediators, Tumor Necrosis Factor, Digestive Diseases, Signal Transduction
Abstract

Background & aimsEosinophilic esophagitis (EoE) is an antigen-mediated eosinophilic disease of the esophagus that involves fibroblast activation and progression to fibrostenosis. Cytokines produced by T-helper type 2 cells and transforming growth factor beta 1 (TGFβ1) contribute to the development of EoE, but other cytokines involved in pathogenesis are unknown. We investigate the effects of tumor necrosis factor superfamily member 14 (TNFSF14, also called LIGHT) on fibroblasts in EoE.MethodsWe analyzed publicly available esophageal CD3+ T-cell single-cell sequencing data for expression of LIGHT. Esophageal tissues were obtained from pediatric patients with EoE or control individuals and analyzed by immunostaining. Human primary esophageal fibroblasts were isolated from esophageal biopsy samples of healthy donors or patients with active EoE. Fibroblasts were cultured; incubated with TGFβ1 and/or LIGHT; and analyzed by RNA sequencing, flow cytometry, immunoblots, immunofluorescence, or reverse transcription polymerase chain reaction. Eosinophils were purified from peripheral blood of healthy donors, incubated with interleukin 5, cocultured with fibroblasts, and analyzed by immunohistochemistry.ResultsLIGHT was up-regulated in the esophageal tissues from patients with EoE, compared with control individuals, and expressed by several T-cell populations, including T-helper type 2 cells. TNF receptor superfamily member 14 (TNFRSF14, also called HVEM) and lymphotoxin beta receptor are receptors for LIGHT that were expressed by fibroblasts from healthy donors or patients with active EoE. Stimulation of esophageal fibroblasts with LIGHT induced inflammatory gene transcription, whereas stimulation with TGFβ1 induced transcription of genes associated with a myofibroblast phenotype. Stimulation of fibroblasts with TGFβ1 increased expression of HVEM; subsequent stimulation with LIGHT resulted in their differentiation into cells that express markers of myofibroblasts and inflammatory chemokines and cytokines. Eosinophils tethered to esophageal fibroblasts after LIGHT stimulation via intercellular adhesion molecule-1.ConclusionsT cells in esophageal tissues from patients with EoE express increased levels of LIGHT compared with control individuals, which induces differentiation of fibroblasts into cells with inflammatory characteristics. TGFβ1 increases fibroblast expression of HVEM, a receptor for LIGHT. LIGHT mediates interactions between esophageal fibroblasts and eosinophils via ICAM1. This pathway might be targeted for the treatment of EoE.

Published
2020

6. Rigid Substrate Induces Esophageal Smooth Muscle Hypertrophy and EoE Fibrotic Gene Expression

Author

Tkachenko, Eugene, Rawson, Renee, La, Elizabeth, Doherty, Taylor A., Baum, Rachel, Cavagnero, Kellen, Miyanohara, Atsushi, Dohil, Ranjan, Kurten, Richard C., and Aceves, Seema S.

Subjects
Genetic Markers, Esophagus, Calcium-Binding Proteins, Gene Expression, Humans, Muscle, Smooth, Eosinophilic Esophagitis, Hypertrophy, Fibrosis, Article, Up-Regulation
Published
2015

7. Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis

Author

Doherty, Taylor A, Baum, Rachel, Newbury, Robert O, Yang, Tom, Dohil, Ranjan, Aquino, Melissa, Doshi, Ashmi, Walford, Hannah H, Kurten, Richard C, Broide, David H, and Aceves, Seema

Subjects
Adolescent, Allergy, Prostaglandin, Biopsy, Primary Cell Culture, Immunology, Immunophenotyping, Esophagus, Immunologic, Receptors, Humans, Innate, Lymphocyte Count, Antigens, Child, Preschool, Interleukin-13, Immunity, Infant, Eosinophilic Esophagitis, Interleukin-33, Lymphocyte Subsets, CD, Eosinophils, Gene Expression Regulation, Cytokines, Female, Interleukin-5, Signal Transduction
Abstract

Group 2 innate lymphoid cells (ILC2s) produce high levels of IL-5 and IL-13, both of which are important pathogenic mediators in eosinophilic esophagitis (EoE). ILC2s have not been previously described in EoE. Our study demonstrates the novel finding that ILC2s are increased in esophageal biopsies from EoE patients with active disease compared with inactive EoE and non-diseased controls, implicating these cells in EoE pathogenesis.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results