Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype.
Adolescent
Case-Control Studies
Cell Differentiation
Cells, Cultured
Child
Child, Preschool
Eosinophilic Esophagitis
/ immunology
Esophagus
/ immunology
Female
Fibroblasts
/ immunology
Humans
Inflammation Mediators
/ metabolism
Intercellular Adhesion Molecule-1
/ metabolism
Male
Paracrine Communication
Phenotype
Receptors, Tumor Necrosis Factor, Member 14
/ metabolism
Signal Transduction
T-Lymphocytes
/ immunology
Tumor Necrosis Factor Ligand Superfamily Member 14
/ genetics
Up-Regulation
Eosinophilia
Fibrogenesis
Fibrosis
ICAM1
Immune Regulation
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
27
01
2020
revised:
07
06
2020
accepted:
18
07
2020
pubmed:
28
7
2020
medline:
13
4
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
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. We analyzed publicly available esophageal CD3 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. 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.
Sections du résumé
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
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.
Identifiants
pubmed: 32712105
pii: S0016-5085(20)34997-0
doi: 10.1053/j.gastro.2020.07.035
pmc: PMC7726704
mid: NIHMS1615942
pii:
doi:
Substances chimiques
ICAM1 protein, human
0
Inflammation Mediators
0
Receptors, Tumor Necrosis Factor, Member 14
0
TNFRSF14 protein, human
0
TNFSF14 protein, human
0
Tumor Necrosis Factor Ligand Superfamily Member 14
0
Intercellular Adhesion Molecule-1
126547-89-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1778-1792.e13Subventions
Organisme : NIAID NIH HHS
ID : K24 AI135034
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI092135
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114457
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119850
Pays : United States
Informations de copyright
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.