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

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 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.