Evidence map›Paper›PMID 34687736›Full record

ArticleGastroenterology2022

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk.

Tetsuo Shoda, Ting Wen, Julie M Caldwell, Netali Ben-Baruch Morgenstern, Garrett A Osswald, Mark Rochman, Lydia E Mack, Jennifer M Felton, J Pablo Abonia, Nicoleta C Arva and 21 more

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. The oesophagus as an immune organ.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Eosinophilic esophagitis: Current concepts in diagnosis and management.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2024
    Review
  15. Article
  16. Review
  17. Development and dysfunction of structural cells in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2024
    Review
  18. Review
  19. Review
  20. Eosinophilic esophagitis: Shifting immune complexity beyond the eosinophil.The Journal of allergy and clinical immunology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 18 institutions in 1 country.

Tetsuo ShodaDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Ting WenDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Julie M CaldwellDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Netali Ben-Baruch MorgensternDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Garrett A OsswaldDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Mark RochmanDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Lydia E MackDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Jennifer M FeltonDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
J Pablo AboniaDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Nicoleta C ArvaDepartment of Pathology, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Dan AtkinsSection of Pediatric Allergy and Immunology, Children's Hospital Colorado, Aurora, Colorado.
Peter A BonisDivision of Gastroenterology, Tufts Medical Center, Boston, Massachusetts.
Kelley E CapocelliDepartment of Pathology, Children's Hospital Colorado, Aurora, Colorado.
Margaret H CollinsDivision of Pathology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Evan S DellonDivision of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Gary W FalkDivision of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Nirmala GonsalvesDivision of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Sandeep K GuptaDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Indianapolis, Indiana.
Ikuo HiranoDivision of Gastroenterology & Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
John LeungDivision of Gastroenterology, Tufts Medical Center, Boston, Massachusetts.
Paul A Menard-KatcherDivision of Gastroenterology and Hepatology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado.
Vincent A MukkadaDivision of Gastroenterology, Hepatology, and Nutrition, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Philip E PutnamDivision of Gastroenterology, Hepatology, and Nutrition, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Amanda K Rudman SpergelDivision of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Jonathan M SpergelDivision of Allergy and Immunology, University of Pennsylvania Perelman School of Medicine/Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Joshua B WechslerGastroenterology, Hepatology and Nutrition, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
Guang-Yu YangDepartment of Pathology and Laboratory Medicine, Northwestern University, Chicago, Illinois.
Seema S AcevesDivision of Allergy Immunology, Departments of Pediatrics and Medicine, University of California, San Diego, Rady Children's Hospital, San Diego, California.
Glenn T FurutaSection of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
Marc E RothenbergDivision of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Rothenberg@cchmc.org.
Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group
Cincinnati Children's Hospital Medical Center · USUniversity of Cincinnati · USNorthwestern University · USLurie Children's Hospital · USTufts Medical Center · USChildren's Hospital Colorado · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · USHospital of the University of Pennsylvania · USUniversity of North Carolina at Chapel Hill · USUniversity of Pennsylvania · USChildren's Hospital of Philadelphia · USIndiana University – Purdue University Indianapolis · USIndiana University School of MedicineNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USRady Children's Hospital-San Diego · USUniversity of California, San Diego · US

Funding

The Impact of COVID-19 on People Living with Rare Diseases and Their FamiliesU2CTR002818 · NCATS · CINCINNATI CHILDRENS HOSP MED CTR · PI Maurizio Macaluso · 2019 to 2026
$51.2M
Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
TRAINING (CAREER DEVELOPMENT) COMPONENTU54AI117804 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI GLENN T FURUTA, Marc E. Rothenberg · 2014 to 2026
$18.5M
Combinatory Effects of Genetic Variants in Eosinophilic EsophagitisK99AI158660 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI SHODA, TETSUO · 2021 to 2022
$261k
NCATS NIH HHS U2C TR002818NIAID NIH HHS K99 AI158660NIAID NIH HHS U54 AI117804NIDDK NIH HHS P30 DK078392
6 · The paper itself

Abstract

BACKGROUND &

aimsEosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences.

methodsEsophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE Endoscopic Reference Score, EoE Histology Scoring System, EoE Diagnostic Panel, and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro.

resultsTSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P < .001). TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System (r = 0.34-0.47, P < .001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P < .001), and genes enriched in cell cycle-related pathways. Interleukin (IL)-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix pathways. Endothelial cell-fibroblast crosstalk induced extracellular matrix changes relevant to esophageal remodeling.

conclusionsPatients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.

Indexed as

AdolescentAdultChildChild, PreschoolEndothelial CellsEosinophilic EsophagitisEsophageal StenosisEsophagusFemaleFibroblastsGene Expression RegulationGene SilencingHumansInterleukin-13MaleMiddle AgedIL13 protein, humanInterleukin-13RNA, Small InterferingTetraspaninsTSPAN12 protein, humanEndotheliumEosinophilEosinophilic EsophagitisFibrosisTranscriptome

Identifiers

PMID34687736
PMCPMC8792211
OpenAlexW3205584737

What OpenQuestion holds

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Registered trials

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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.