Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia
Grace L. Burns, Jessica Bruce, Kyra Minahan, Andrea Mathe, Thomas Fairlie, Raquel Cameron, Crystal Naudin, Prema M. Nair, Michael Potter, Mudar Zand Irani, Steven Bollipo, Robert E. Foster, Lay T. Gan, Ayesha Shah, Natasha A. Koloski, Paul S. Foster, Jay C. Horvat, Martin Veysey, Gerald Holtmann, Nick Powell, Marjorie M. Walker, Nicholas J. Talley, Simon Keely
Abstract
Background Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD. Objective This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology. Methods We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls. Results There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, p =0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, p =0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p =0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p =0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p =0.027) subsets. Peripheral T cell populations were unchanged between FD and control. Conclusion Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.