Inactivation of protein tyrosine phosphatases enhances interferon signaling in pancreatic islets

Abstract

Type 1 diabetes (T1D) is the result of an autoimmune assault against the insulin-producing pancreatic b-cells, where chronic local inflammation (insulitis) leads to b-cell destruction. T cells and macrophages infiltrate into islets early in T1D pathogenesis. These immune cells secrete cytokines that lead to the production of reactive oxygen species (ROS) and T-cell invasion and activation. Cytokine-signaling pathways are very tightly regulated by protein tyrosine phosphatases (PTPs) to prevent excessive activation. Here, we demonstrate that pancreata from NOD mice with islet infiltration have enhanced oxidation/inactivation of PTPs and STAT1 signaling compared with NOD mice that do not have ..