EXPLOITING THE THERAPEUTIC POTENTIAL OF INVARIANT NKT CELLS IN TYPE 1 DIABETES

Type 1 diabetes (T1D) is an autoimmune disease caused by cells of the body’s own immune system that attack pancreatic beta islets. Those self-reactive immune cells are present in healthy people and they should be tightly controlled by regulatory mechanisms to avoid autoimmune disease. A specific cell population of the immune system, named NKT cells, plays a key role in control of immune responses including autoreactive ones. They have the ability to decide whether to start an immune response or turn it off. Recent findings demonstrated that peripheral activation of NKT cells by administration of their specific antigen prevent autoimmune disease in pre-clinical models of T1D and multiple sclerosis. In our previously founded Telethon-JDRF project we found that NOD mice, the animal model of T1D, carry a genetic defect that impairs their ability to induce those regulatory cells. If NKT cell activation protect from T1D, it is counter-deductive that a defect of mechanism that stimulate regulatory NKT cells should lead to autoimmune diabetes. Hence, we aim to correct the genetic defect in NOD mice through gene therapy and cellular therapy and to assess whether this therapeutic approach will cure T1D in mice. In parallel, we will analyze whether the same genetic defect can be found in Type 1 Diabetic patients and their “at risk” relatives. A cure for T1D should aim to correct the pathways that are responsible for the immune attack to insulin-secreting cells of the pancreas. Specifically, we should promote the restoration of regulatory mechanisms that prevent or block the autoimmune attack to the islets and are defective in T1D patients We believe our study could provide a new therapeutic approach to restore defective function of regulatory cells and preserve beta cell mass in early-diagnosed patients or improve survival of islet grafts in transplanted T1D patients.