Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia

Abstract

BackgroundFunctional 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.ObjectiveThis study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology.MethodsWe 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.ResultsThere 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.ConclusionOur 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.

Research trends in the field of the gut-brain interaction: Functional dyspepsia in the spotlight – An integrated bibliometric and science mapping approach

“…In light of recent reports of increased mucosal Th17 density in pediatric FD patients with chronic gastritis ( Singh et al, 2020 ), it may be possible to explain at least some of the symptoms of this condition by Th17 cytokine responses ( Keely et al, 2015 ; Burns et al, 2019a ). The most recent work by Burns et al (2023) shows that FD patients have elevated Th2- and Th17-like cells localized to the duodenum, implying that dual lymphocyte response pathways are implicated in the generation of FD symptoms. In addition, the existence of effector and memory cells indicates that the microinflammation in FD is antigen driven ( Burns et al, 2023 ).…”

“…The most recent work by Burns et al (2023) shows that FD patients have elevated Th2- and Th17-like cells localized to the duodenum, implying that dual lymphocyte response pathways are implicated in the generation of FD symptoms. In addition, the existence of effector and memory cells indicates that the microinflammation in FD is antigen driven ( Burns et al, 2023 ). Taken together, the interplay between Th2- and Th17-signaling and ILC2-mediated inflammatory signals may be hallmarks of immune activation profile in the text of FD ( Keely et al, 2015 ).…”

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

“…Written informed consent was received before participation. Participants (aged 18–80 years) were recruited from outpatient gastroenterology clinics at John Hunter, Gosford and Wyong Hospitals in New South Wales, and Princess Alexandra Hospital, Brisbane, Queensland, Australia, as part of a larger study investigating immune activation in FD ( 25 ). Controls were requiring endoscopy but asymptomatic for FD-associated symptoms.…”

Tunable PhenoCycler imaging of the murine pre-clinical tumour microenvironments

“…Reporters are complementary oligonucleotides to the unique barcodes, and are tagged with either fluorophores ATTO550 AF647, or AF750. As of this writing, PhenoCycler has been used to image up to 101 different markers in single tissue [ 15 , 16 ], and has been used to spatially profile human cancers such as cutaneous T cell lymphoma [ 17 ], follicular lymphoma [ 18 ], diffuse large B cell lymphoma [ 19 ], Hodgkin’s lymphoma [ 20 ], bladder cancer [ 21 ], colorectal cancer [ 22 ], basal cell carcinoma [ 23 ], glioblastoma [ 24 ], breast cancer [ 25 ], and head and neck squamous cell carcinoma [ 26 ], and human non-cancerous conditions such as ulcerative colitis [ 27 ], diabetic nephropathy [ 28 ], functional dyspepsia [ 29 ], vitiligo [ 30 ], and Alzheimer’s disease [ 31 ].…”