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TRAV26-2 T 细胞受体表达与功能性消化不良患者对小麦蛋白的黏膜淋巴细胞反应相关。

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

机构信息

School of Biomedical Sciences & Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, Australia.

NHMRC Centre of Research Excellence in Digestive Health, University of Newcastle, Newcastle, Australia.

出版信息

Clin Transl Gastroenterol. 2023 Dec 1;14(12):e00638. doi: 10.14309/ctg.0000000000000638.

DOI:10.14309/ctg.0000000000000638
PMID:37753952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10749711/
Abstract

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 patients with FD and 23 controls. LPMCs were exposed to gluten (0.2 mg/mL) or gliadin (0.2 mg/mL) for 24 hours. Flow cytometry was performed to phenotype lymphocytes. Quantitative PCR was used to measure the 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 with that in controls and unstimulated FD LPMCs. Duodenal gene expression of TRAV26- 2 was decreased in patients with FD compared with that in controls. We identified a positive association between gene expression of this T-cell receptor variant and LPMC effector Th17-like cell populations in patients with FD, but not controls after exposure to gluten, but not gliadin.

DISCUSSION

Our findings suggest that gliadin exposure provokes a duodenal effector Th2-like response in patients with FD, supporting the notion that food antigens drive responses in some patients. Furthermore, these findings suggest that altered lymphocyte responses to wheat proteins play a role in FD pathogenesis.

摘要

简介

观察性研究报告显示功能性消化不良(FD)与含小麦食物之间存在关联;然而,尚未证明存在适应性反应。我们研究了小麦中的抗原是否会引起 FD 十二指肠淋巴细胞的反应。

方法

从 50 名 FD 患者和 23 名对照者的十二指肠活检中分离出黏膜固有层单核细胞(LPMCs)。将 LPMCs 暴露于谷蛋白(0.2mg/mL)或麦醇溶蛋白(0.2mg/mL)24 小时。通过流式细胞术对淋巴细胞进行表型分析。采用定量 PCR 测量麦醇溶蛋白相关 T 细胞受体α变异体(TRAV)26-2 的表达。

结果

与对照者和未刺激的 FD LPMCs 相比,FD LPMCs 在对麦醇溶蛋白(而非谷蛋白)刺激时,效应 Th2 样群体增加。与对照者相比,FD 患者的十二指肠 TRAV26-2 基因表达降低。我们发现,在暴露于谷蛋白而非麦醇溶蛋白后,FD 患者的该 T 细胞受体变体的基因表达与 LPMC 效应 Th17 样细胞群体之间存在正相关,但在对照者中则没有。

讨论

我们的研究结果表明,麦醇溶蛋白暴露会引起 FD 患者十二指肠效应 Th2 样反应,支持食物抗原在某些患者中引发反应的观点。此外,这些发现表明,对小麦蛋白的淋巴细胞反应改变在 FD 发病机制中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/edde95c162d0/ct9-14-e00638-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/409ea7393f99/ct9-14-e00638-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/a18e605f4ac9/ct9-14-e00638-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/8556e390330c/ct9-14-e00638-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/b6e46d83267b/ct9-14-e00638-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/edde95c162d0/ct9-14-e00638-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/409ea7393f99/ct9-14-e00638-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/a18e605f4ac9/ct9-14-e00638-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/8556e390330c/ct9-14-e00638-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/b6e46d83267b/ct9-14-e00638-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eda3/10749711/edde95c162d0/ct9-14-e00638-g005.jpg

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