Small Bowel Homing T Cells Are Associated With Symptoms and Delayed Gastric Emptying in Functional Dyspepsia

Adam, Birgit; Liebregts, Tobias; Bredack, Christoph; Brierley, Stuart M.; Hughes, Patrick A.; Blackshaw, L. Ashley; Talley, Nicholas J.; Holtmann, Gerald

doi:10.1016/s0016-5085(11)60565-9

Cited by 2 publications

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“…Given reports of alterations in specific T-cell subpopulations in FD ( 25 , 35 – 37 ), it is possible that TCR variants contribute to low-grade inflammation in FD because binding strength of the MHC-antigen-TCR interaction regulates the strength of an immune response ( 38 , 39 ). There are other variants, including TCR beta (TRBV)7-2 and TRBV9, with demonstrated affinity for immunogenic wheat peptides ( 40 ) and may warrant investigation.…”

Section: Discussionmentioning

confidence: 99%

TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia

Burns,

Potter,

Mathe

et al. 2023

Clin Transl Gastroenterol

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Introduction: An association between functional dyspepsia (FD) and wheat-containing foods has been reported in observational studies, however, an adaptive response has not been demonstrated. We examined whether antigens present in wheat could provoke a response from FD duodenal lymphocytes. Methods: Lamina propria mononuclear cells (LPMCs) were isolated from duodenal biopsies from 50 FD patients and 23 controls. LPMCs were exposed to gluten (0.2mg/mL) or gliadin (0.2mg/mL) for 24 hours. Flow cytometry was performed to phenotype lymphocytes. qPCR was used to measure expression of gliadin-associated T-cell receptor alpha variant (TRAV)26-2. Results: In response to gliadin (but not gluten) stimulation, the effector Th2-like population was increased in FD LPMCs compared to controls and unstimulated FD LPMCs. Duodenal gene expression of TRAV26-2 was decreased in FD compared to controls. We identified a positive association between gene expression of this T cell receptor variant and LPMC effector Th17-like cell populations in FD patients, but not controls following exposure to gluten, but not gliadin. Conclusion: Our findings suggest that gliadin exposure provokes a duodenal effector Th2-like response in FD patients, supporting the notion that food antigens drive responses in some patients. Further, these findings suggest that altered lymphocyte responses to wheat proteins play a role in FD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia

Burns,

Potter,

Mathe

et al. 2023

Clin Transl Gastroenterol

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Integrating Network Pharmacology and In Vivo Model to Investigate the Mechanism of Biheimaer in the Treatment of Functional Dyspepsia

Wang

Huanbieke

Cai

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Biheimaer (BHM) is a hospital formulation for clinical treatment of dyspepsia and acid reflux, based on Compatibility Theory of Traditional Chinese Medicine. This study anticipated to elucidate the molecular mechanism of BHM against Functional dyspepsia via combined network pharmacology prediction with experimental verification. Methods. Based on network pharmacology, the potential active components and targets of BHM in the treatment of functional dyspepsia were explored by prediction and molecular docking technology. The results of protein–protein interaction analysis, functional annotation, and pathway enrichment analysis further refined the main targets and pathways. The molecular mechanism of BHM improving functional dyspepsia mice induced by L-arginine + atropine was verified on the basis of network pharmacology. Results. In this study, 183 effective compounds were screened from BHM; moreover, 1007 compound-related predicted targets and 156 functional dyspepsia-related targets were found. The results of enrichment analysis and in vivo experiments showed that BHM could regulate intestinal smooth muscle contraction to play a therapeutic role in functional dyspepsia by reducing the expression of NOS3, SERT, TRPV1, and inhibiting the inflammatory cytokine (IL-1β, TNF-α) to intervene the inflammatory response in mice. Conclusions. This study revealed the molecular biological mechanisms of the Traditional Chinese Medicine formulation of BHM in functional dyspepsia by network pharmacology and experimental verification, meanwhile provided scientific support for subsequent clinical medication.

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Small Bowel Homing T Cells Are Associated With Symptoms and Delayed Gastric Emptying in Functional Dyspepsia

Cited by 2 publications

References 0 publications

TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia

TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia

Integrating Network Pharmacology and In Vivo Model to Investigate the Mechanism of Biheimaer in the Treatment of Functional Dyspepsia

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