Project 459049

Type 1 diabetes (T1D) is an incurable, life-long autoimmune disease that affects ~300,000 Canadians. In T1D, the immune system attacks and destroys beta cells in the pancreas that normally produce insulin, a hormone that controls blood sugar levels. As such, people with T1D must constantly monitor their blood sugar and regularly inject insulin, as high blood sugar can cause damage to organs, blood vessels, and nerves. Regulatory T cells (Treg) are immune cells that naturally control immune responses and help repair damaged cells. In T1D, Tregs can become dysfunctional, reducing their ability to suppress immune attacks against beta cells and to repair beta cell damage. However, Tregs and other immune cells are very hard to study in this context because they are relatively rare in the pancreas and have many functions in the body. Because of their rarity, the mechanism of Treg dysfunction in T1D remains unclear. Our project aims to address this problem. We will study Tregs as a cellular therapy for T1D to better understand their role and test their effects on beta cell repair. To do this, we will compare between pancreatic cells from non-diabetic and T1D organ donors. We will isolate beta cells from these pancreases and analyse which genes are being expressed in the surrounding tissue to identify what kinds of immune cells reside in the pancreas, describe what they do, and learn how they communicate with one another. The second part of this project will explore whether healthy Tregs help the body repair dysfunctional beta cells. We will culture healthy Tregs with dysfunctional beta cells to learn whether they can potentially support beta cell regeneration. These findings may lead us to better understand how Treg cellular therapies for T1D can best be delivered, and how we can use them to support treatment, prevention, and curative options for T1D. It will also reveal insights into the immune environment of the pancreas, which has not been rigorously described.