Expansion Of Th17 Cells And Functional Defects In T Regulatory Cells Are Key Features Of The Pancreatic Lymph Nodes In Patients With Type 1 Diabetes

Type 1 diabetes is believed to have a Th17-cell (auto-aggressive) bias and/or a T regulatory cell (Treg-suppessive/beneficial) defect. Understanding whether this is a hallmark of patients with type 1 diabetes is a crucial question that remains unsolved, largely due to the difficulties of accessing tissues targeted by the disease. In this study, the investigators characterized Th17 cells and Tregs residing in the pancreatic-draining lymph nodes (PLNs) of 19 patients with type 1 diabetes and 63 nondiabetic donors and those circulating in the peripheral blood of 14 type 1 diabetic patients and 11 healthy subjects. Both the 19 patients with type 1 diabetes from whom PLNs were collected as well as the 14 type 1 diabetic patients from whom peripheral blood was collected have long-standing T1D. Increased numbers of Th17 cells as well as functional defects in Tregs were found in the PLNs of long standing type 1 diabetic subjects but not in their peripheral blood. In addition, there were lower numbers of Tregs in the PLNs of type 1 diabetic subjects and these Tregs had an impaired suppressive capability. Importantly, this imbalance in Treg number or function was not observed in the patients’ peripheral blood.

Reference:

Ferraro, A., et al. (2011). Expansion of Th17 Cells and Functional Defects in T Regulatory Cells Are Key Features of the Pancreatic Lymph Nodes in Patients With Type 1 Diabetes. Diabetes. 60:2903-2913.

Ramifications for Individuals with Type 1 Diabetes:

This research clearly strongly indicates that the immune signature of long standing T1D may well be different from other stages of the disease and suggests that over time, the immune dysfunction becomes more local than peripheral. Importantly, this study confirms results from pre-clinical models that the Treg/Th17 balance could be key in controlling T1D and likely other autoimmune diseases.

JDRF Involvement:

This trial was funded by JDRF.