IntroductionSubstance 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.MethodsDistal 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.ResultsNK1R was expressed on epithelial cells and, rarely, on CD3+ T cells.
Frontiers in Immunology published a clinical update in Infectious Disease on 27 Apr 2026.
The item focuses on Neuro-immune-epithelial pathways involving substance P may contribute to mucosal pathology in gastro-oesophageal reflux disease.
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