Retraining the Autoimmune System in Type 1 Diabetes
Tom Serwold, Ph.D.
In the autoimmune attack behind type 1 diabetes, you can think of T cells as an improperly trained SWAT team that hones in on insulin-producing beta cells rather than pathogens. Research at Joslin seeks to sort out the diabolically complicated details of their attack and to work toward steps that can be taken to stop it.
In one project, Thomas Serwold, Ph.D., employs mouse models to understand the cells within the thymus that help T cells to develop, and whether these cells can be altered to prevent autoimmune T cells from developing in the first place.
“Throughout life, T cells are produced in the thymus, each with a unique receptor that can bind only to certain protein fragments derived from pathogens,” explains Dr. Serwold. “Also within the thymus, epithelial cells act like teacher cells for the T cells, preventing those that might target the body’s own cells from graduating and leaving the thymus.”
“Developing techniques to manipulate the functions of these teacher cells will tell us a lot about how the autoimmune T cells that drive type 1 diabetes come to develop, and how they might be eliminated,” he adds.
In related Joslin work, Tihamer Orban, M.D., is a principal investigator in TrialNet and the Immune Tolerance Network, national networks dedicated to translating basic research into wider clinical application for prediction, prevention and intervention for type 1 diabetes autoimmunity. A novel vaccine developed by Dr. Orban, designed to induce an immune response that calls in regulatory T cells that protect against the type 1 attack, is in clinical trials.
Studying autoimmunity some years back, Myra Lipes, M.D., made a surprising discovery when she genetically modified mice to express a high-risk human type 1 diabetes susceptibility gene. “In addition to developing diabetes, the mice developed autoimmune heart disease,” she says. Following up, her lab has identified a molecule that may spark this autoimmune attack, potentially pointing toward a new approach to diagnosing and treating heart disease in patients with type 1 diabetes.
“Curing an autoimmune disease such as type 1 diabetes is like solving a very difficult jigsaw puzzle,” says Aldo Rossini, M.D., Mary K. Iacocca Senior Visiting Scholar at Joslin. “With every little piece of the puzzle, we’re getting closer and closer to understanding the problem. Today Joslin is building up the immunobiology group with bright young researchers from multiple fields. One day, the final pieces of the puzzle will be there.”