Evidence map›Paper›PMID 26992000›Full record

ArticlePloS one2016

Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE).

Prasanna M Chandramouleeswaran, Dawen Shen, Anna J Lee, Alain Benitez, Kara Dods, Fiona Gambanga, Benjamin J Wilkins, Jamie Merves, Yuliana Noah, Sarit Toltzis and 6 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
6.0field-weighted citation impact, top 4% 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

33 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Mouse models of eosinophilic esophagitis: molecular and translational insights.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Review
  9. Review
  10. Animal models of eosinophilic esophagitis.Journal of leukocyte biology · 2024
    Review
  11. Development and dysfunction of structural cells in eosinophilic esophagitis.The Journal of allergy and clinical immunology · 2024
    Review
  12. Barrier Dysfunction in Eosinophilic Esophagitis.Current gastroenterology reports · 2023
    Review
  13. Article
  14. Eosinophilic Esophagitis-What Do We Know So Far?Journal of clinical medicine · 2023
    Review
  15. EoE behaves as a unique Th2 disease: a narrative review.Translational gastroenterology and hepatology · 2023
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
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

16 authors at 3 institutions in 1 country.

Prasanna M ChandramouleeswaranDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Dawen ShenDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Anna J LeeDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Alain BenitezDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Kara DodsDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Fiona GambangaDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Benjamin J WilkinsDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States of America.
Jamie MervesDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Yuliana NoahDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Sarit ToltzisDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Jennifer H YearleyDepartment of Immunology, Merck Research Labs, Palo Alto, California 94304, United States of America.
Jonathan M SpergelDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States of America.
Hiroshi NakagawaDivision of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States of America.
Rene deWaal MalefytDepartment of Immunology, Merck Research Labs, Palo Alto, California 94304, United States of America.
Amanda B MuirDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Mei-Lun WangDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States of America.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · USMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GARY D. WU · 1997 to 2026
$32.5M
TRAINING (CAREER DEVELOPMENT) COMPONENTU54AI117804 · NIAID · CINCINNATI CHILDRENS HOSP MED CTR · PI JONATHAN Micheal SPERGEL · 2014 to 2026
$18.5M
Toll-like Receptor Signaling in the Esophageal EpitheliumR01DK087789 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI SPERGEL, JONATHAN MICHEAL · 2010 to 2014
$1.8M
Lysyl oxidase mediated fibrosis in eosinophilic esophagitisK08DK106444 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI MUIR, AMANDA BROOKE · 2015 to 2019
$778k
Role of Cirhin/Utp4 in biliary development and diseaseK08DK099379 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI WILKINS, BENJAMIN J · 2014 to 2018
$737k
NIAID NIH HHS U54 AI117804NIDDK NIH HHS 1K08DK106444-01NIDDK NIH HHS DK-50306NIDDK NIH HHS K08 DK099379NIDDK NIH HHS K08 DK106444NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK087789NIDDK NIH HHS R01 DK087789-02S1
6 · The paper itself

Abstract

Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2-type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (≥15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control subjects, and found that TSLP expression was restricted to the differentiated suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent with these results in vivo, inducible TSLP protein secretion was higher in CaCl2 differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT) compared to undifferentiated cells of the basal phenotype, following stimulation with the TLR3 ligand poly(I:C). To determine whether food antigens could directly induce epithelial TSLP secretion, differentiated and undifferentiated primary esophageal epithelial cells from EoE and non-EoE subjects were challenged with food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced TSLP secretion in differentiated epithelial cells from both EoE and control cell lines, an effect abolished by budesonide and NF-κb inhibition. Together, our study shows that specific food antigens can trigger innate immune mediated esophageal TSLP secretion, suggesting that esophageal epithelial cells at the barrier surface may play a significant role in the pathogenesis of EoE by regulating TSLP expression.

Indexed as

Cell DifferentiationAntigensBudesonideCell Line, TransformedCytokinesEosinophilic EsophagitisEpithelial CellsEsophagusGene Expression RegulationHumansNF-kappa BPoly I-CThymic Stromal LymphopoietinToll-Like Receptor 3AntigensBudesonideCytokinesNF-kappa BPoly I-CThymic Stromal LymphopoietinTLR3 protein, humanToll-Like Receptor 3

Identifiers

PMID26992000
PMCPMC4798725
OpenAlexW2304299091

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.