Evidence map›Paper›PMID 42125661›Full record

ArticleFrontiers in immunology2026

Neuro-immune-epithelial pathways involving substance P may contribute to mucosal pathology in gastro-oesophageal reflux disease.

Tom Leech, Philip Woodland, Madusha Peiris

Abstract read
In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

3 authors.

Tom LeechWingate Institute of Neurogastroenterology, Blizard Institute, The Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Philip WoodlandWingate Institute of Neurogastroenterology, Blizard Institute, The Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Madusha PeirisWingate Institute of Neurogastroenterology, Blizard Institute, The Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Substance P (SP) is contained in nerve fibres innervating the oesophageal mucosa and is released into the mucosa during oesophageal acid perfusion. However, the downstream effects of this peripheral SP are not known. We investigated the expression of SP receptors in the oesophageal mucosa of healthy controls and GORD patients, localisation of mast cells in relation to SP+ nerve fibres, and effects of SP exposure on oesophageal epithelial cells. Methods: Distal oesophageal biopsies were collected from healthy controls (HC; N = 10), functional heartburn (FH; N = 10), non-erosive reflux disease (NERD; N = 14), and erosive reflux disease (ERD; N = 13) patients. IHC was used to determine the cellular expression of the SP receptor, NK1R, on E-Cadherin+, CD3+, and tryptase+ cells. NE-1 oesophageal epithelial cells were incubated with SP to investigate inflammatory pathway activation. The proportion and density of mast cells expressing an SP receptor, MRGPRX2, was analysed, and the distance between SP+ nerve fibres and mast cells was determined. Results: NK1R was expressed on epithelial cells and, rarely, on CD3+ T cells. NK1R fluorescence intensity was significantly higher in NERD and ERD oesophageal mucosa compared with HCs. In NE-1 cells, exposure to SP induced NF-κB phosphorylation, ameliorated by NK1R inhibition, and release of IL-6 and IL-8. In NERD and ERD mucosa, the density of MRGPRX2+ mast cells was significantly higher than HCs. Across all subjects, 25 SP+ nerves were detected; 32% were located within 10 µm of a mast cell, and 84% within 50 µm. Conclusion: Expressions of SP receptors NK1R and MRGPRX2 are upregulated in NERD and ERD oesophageal mucosa, on epithelial cells and mast cells, respectively. Mast cells are also closely apposed to SP+ nerve fibres in the oesophageal mucosa. Furthermore, SP directly induced inflammatory pathway activation and release of cytokines in oesophageal epithelial cells

Indexed as

Epithelial CellsEsophageal MucosaGastroesophageal RefluxNeuroimmunomodulationSubstance PAdultFemaleHumansMaleMast CellsMiddle AgedNerve FibersReceptors, Neurokinin-1Signal TransductionReceptors, Neurokinin-1Substance Pgastro-oesophageal reflux diseaseinflammationmast cellsneuro-immunesubstance P

Identifiers

PMID42125661
PMCPMC13158196

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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.