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.

中文翻译：

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TRAV26-2 T 细胞受体表达与功能性消化不良患者粘膜淋巴细胞对小麦蛋白的反应相关。

引言 观察性研究报道了功能性消化不良（FD）与含小麦食品之间的关联，但适应性反应尚未得到证实。我们检查了小麦中存在的抗原是否可以引起 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固有层单核细胞 (LPMC)。将 LPMC 暴露于麸质 (0.2mg/mL) 或麦醇溶蛋白 (0.2mg/mL) 24 小时。采用流式细胞术对淋巴细胞进行表型分析。qPCR 用于测量麦醇溶蛋白相关 T 细胞受体 α 变体 (TRAV)26-2 的表达。结果 与对照和未刺激的 FD LPMC 相比，响应于麦醇溶蛋白（但不是麸质）刺激，FD LPMC 中的效应 Th2 样细胞群有所增加。与对照组相比，FD 中 TRAV26-2 的十二指肠基因表达降低。我们发现 FD 患者中这种 T 细胞受体变体的基因表达与 LPMC 效应器 Th17 样细胞群之间存在正相关，但在接触麸质（但不是麦醇溶蛋白）后的对照中则不然。结论 我们的研究结果表明，麦醇溶蛋白暴露会在 FD 患者中引发十二指肠效应器 Th2 样反应，支持食物抗原在某些患者中驱动反应的观点。此外，这些发现表明淋巴细胞对小麦蛋白反应的改变在 FD 发病机制中发挥着作用。