Pathway Scientist Identifies Possible Trigger for Type 1 Diabetes
Type 1 diabetes occurs when the body's immune system attacks and destroys the insulin-producing cells in the pancreas. There is no cure for type 1 diabetes, which affects about 1.25 million Americans.
In order to prevent or reverse the development of type 1 diabetes, it is essential to understand why and how the immune system attacks the body's own cells.
The American Diabetes Association awarded one of its highly-competitive Pathway to Stop Diabetes grants to Thomas Delong, PhD, in 2015 to seek answers to these questions.
Dr. Delong coauthored a study published today in the prestigious journal Science describing results from his American Diabetes Association-funded project, which provide a possible explanation for how the immune system goes awry leading to type 1 diabetes.
The immune system's "T cells" normally fight infections. T cells identify markers called "antigens" on the surface of viruses and bacteria and then mount an attack. In healthy people, the body's own cells are protected from the immune system because T cells do not recognize self-antigens. However, in type 1 diabetes and other autoimmune diseases, something in this protective system breaks down.
Dr. Delong and colleagues isolated T cells from a mouse model of type 1 diabetes to determine what it may be that they recognize as foreign in insulin-producing cells. Using this approach, they identified a modification of insulin that acted as an antigen. They found that the so-called "hybrid insulin peptides" (HIPs) were recognized by immune T cells from pancreatic islets of two organ donors who had type 1 diabetes, as well. This study suggests that these HIPs may play an important role in triggering the immune system to attack the body's insulin-producing cells, causing type 1 diabetes.
Understanding the misguided immune attack is a critical first step in identifying possible ways to turn it off, which may offer insight into new therapies to prevent or reverse type 1 diabetes.
Dr. Delong, who himself has type 1 diabetes, appeared on CBS Denver News to explain this exciting study.
Delong T, Wiles TA, Baker RL, Bradley B, Barbour G, Reisdorph R, Armstrong M, Powell RL, Reisdorph N, Kumar N, Elso CM, DeNicola M, Bottino R, Powers AC, Harlan DM, Kent SC, Mannering SI, Haskins K. Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion. Science. 351(6274): 676-8.