CD39 and diabetes
Children diagnosed with type 1 diabetes (T1D) show signs of low CD39+/CD45RA+ Treg cells, which may indicate loss of its suppressive function [166]. Lower expression of CD39 in memory Tregs has been reported as a potential mechanism explaining the defective suppressive function of Tregs in T1D patients [167]. The percentages of CD39+ and CD39+CD19+ cells were associated with glycated hemoglobin and fasting plasma glucose levels. CD39+ cells might have a balancing regulatory role in the inflammatory process observed in patients with type 2 diabetes (T2D)[168]. The T2D patients with obesity showed significantly lower percentages of CD39+ Treg cells and a negative correlation between CD39+ Treg cells and weight, and body mass index was detected[169]. Mesenchymal stem cells from human gingiva can migrate to the pancreas and local lymph nodes and act through the CD39/CD73 pathway to regulate effector T-cells. Infusion of GMSCs significantly controlled blood glucose levels, delayed diabetes onset, and ameliorated pathology scores in pancreas[170]. CD39 KO mice developed diabetes more rapidly and with higher frequency than WT mice, while CD39 overexpressing mice were protected. Furthermore, adoptive transfer experiments indicated that tissue-restricted overexpression of CD39 conferred robust protection, suggesting that this may be a useful strategy to protect islet grafts from T cell-mediated injury[171].