Evidence map›Paper›PMID 39617290›Full record

ArticleThe Journal of allergy and clinical immunology2025

Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction.

Medet Jumabay, Edsel M Abud, Kevin Okamoto, Paramita Dutta, Austin W T Chiang, Haining Li, Mario C Manresa, Yanfang P Zhu, Dana Frederick, Richard Kurten and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of allergy and clinical immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Medet JumabayDepartment of Pediatrics, University of California, San Diego, Calif; Division of Allergy Immunology, University of California, San Diego, Calif.
Edsel M AbudDepartment of Pediatrics, University of California, San Diego, Calif; Division of Allergy Immunology, University of California, San Diego, Calif; Scripps Clinic, San Diego, Calif; Scripps Research Translational Institute, San Diego, Calif.
Kevin OkamotoDepartment of Pediatrics, University of California, San Diego, Calif; Division of Allergy Immunology, University of California, San Diego, Calif.
Paramita DuttaLa Jolla Institute, La Jolla, Calif.
Austin W T ChiangDepartment of Pediatrics, University of California, San Diego, Calif; Department of Bioengineering, University of California, San Diego, Calif.
Haining LiDepartment of Pediatrics, University of California, San Diego, Calif; Scripps Clinic, San Diego, Calif.
Mario C ManresaDepartment of Pediatrics, University of California, San Diego, Calif; Division of Allergy Immunology, University of California, San Diego, Calif.
Yanfang P ZhuDepartment of Pediatrics, University of California, San Diego, Calif.
Dana FrederickArkansas Children's Hospital, Little Rock, Ark.
Richard KurtenDepartment of Bioengineering, University of California, San Diego, Calif.
Ben CrokerDepartment of Pediatrics, University of California, San Diego, Calif.
Nathan E LewisDepartment of Pediatrics, University of California, San Diego, Calif; Scripps Clinic, San Diego, Calif.
Joshua L KennedyArkansas Children's Hospital, Little Rock, Ark.
Ranjan DohilDepartment of Pediatrics, University of California, San Diego, Calif; Division of Gastroenterology, University of California, San Diego, Calif; La Jolla Institute, La Jolla, Calif.
Michael CroftLa Jolla Institute, La Jolla, Calif.
Ferhat AyDepartment of Pediatrics, University of California, San Diego, Calif; La Jolla Institute, La Jolla, Calif.
Joshua B WechslerLurie Children's Hospital, Northwestern University, Chicago, Ill.
Seema S AcevesDepartment of Pediatrics, University of California, San Diego, Calif; Division of Allergy Immunology, University of California, San Diego, Calif; Division of Gastroenterology, University of California, San Diego, Calif; Department of Medicine, University of California, San Diego, Calif; Lurie Children's Hospital, Northwestern University, Chicago, Ill. Electronic address: saceves@health.ucsd.edu.

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
Innate immune mechanisms of the host response to CoccidioidesU19AI166059 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Joshua Fierer · 2022 to 2026
$10.0M
Institutional Career Development CoreKL2TR002552 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI NICHOLSON, LAURA · 2018 to 2022
$5.2M
Studying the function of human genetic variation in the light of 3D genome organizationR35GM128938 · NIGMS · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI Ferhat Ay · 2018 to 2026
$4.6M
TWEAK/TNFSF12 and LIGHT/TNFSF14 interactions in allergic esophagitis remodelingR01DK114457 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Seema S Aceves, Ferhat Ay · 2018 to 2026
$4.5M
Mechanisms of tissue damage leading to chronic allergic eosinophilic esophagitisR01AI092135 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACEVES, SEEMA S · 2011 to 2020
$4.4M
Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3M
CTSA K12 Program at The Scripps Research InstituteK12TR004410 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI Laura Nicholson, Athena Philis-Tsimikas · 2023 to 2026
$3.9M
Mentoring Patient Oriented Research in Allergic Eosinophilic Gastrointestinal DisordersK24AI135034 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACEVES, SEEMA S · 2018 to 2022
$898k
Contribution of rigid matrix to allergic eosinophilic esophagitis pathogenesisR56AI092135 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACEVES, SEEMA S · 2023 to 2023
$198k
NCATS NIH HHS K12 TR004410NCATS NIH HHS KL2 TR002552NCATS NIH HHS UL1 TR001442NIAID NIH HHS K24 AI135034NIAID NIH HHS R01 AI092135NIAID NIH HHS R56 AI092135NIAID NIH HHS U19 AI166059NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK114457NIGMS NIH HHS R35 GM119850NIGMS NIH HHS R35 GM128938
6 · The paper itself

Abstract

backgroundPathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE-associated tissue remodeling causes clinical dysphagia, food impactions, esophageal rigidity, and strictures, molecular mechanisms driving these complications remain under investigation.

objectiveWe hypothesized that chronic EoE inflammation induces pathogenic fibroblasts with dysfunctional tissue regeneration and motility.

methodsWe used single-cell RNA sequencing, fluorescence-activated cell sorting analysis, and fibroblast differentiation and migration assays to decipher the induced and retained pathogenic dysfunctions in EoE versus healthy esophageal fibroblasts.

resultsDifferentiation assays demonstrated that active EoE fibroblasts retain regenerative programs for rigid cells such as chondrocytes (P < .05) but lose healthy fibroblast capacity for soft cells such as adipocytes (P < .01), which was reflected in biopsy sample immunostaining (P < .01). EoE, but not healthy, fibroblasts show proinflammatory and prorigidity transcriptional programs on single-cell RNA sequencing. In vivo, regenerative fibroblasts reside in perivascular regions and near the epithelial junction, and during EoE, they have significantly increased migration (P < .01). Flow analysis and functional assays demonstrated that regenerative EoE fibroblasts have decreased surface CD73 expression and activity (both P < .05) compared to healthy controls, indicating aberrant adenosine triphosphate handling. EoE fibroblast dysfunctions were induced in healthy fibroblasts by reducing CD73 activity and rescued in EoE using adenosine repletion.

conclusionA normalization of perturbed extracellular adenosine triphosphate handling and CD73 could improve pathogenic fibroblast dysfunction and tissue regeneration in type 2 inflammatory diseases.

Indexed as

Eosinophilic EsophagitisEsophagusFibroblastsRegenerationAnimalsCell DifferentiationCell MovementCells, CulturedFemaleHumansMaleadenosineATPCD73Eosinophilic esophagitisfibrosisremodeling

Identifiers

PMID39617290
PMCPMC11980045

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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.