Grant: Doctoral Research Award: Canada Graduate Scholarships

Type 1 diabetes (T1D) is an autoimmune disease that occurs when the immune system destroys insulin-producing cells, known as beta cells. Beta cells are found in clusters, called islets, so islet transplantation is an option to restore insulin production and decrease disease burden. However, as with all transplants, recipients must take immune-suppressing drugs to prevent their immune system from attacking the transplanted cells as foreign material. These drugs are required over a person's lifetime and place the recipient at much higher risk of infections and cancer. An alternative to these drugs is regulatory T cells (Tregs), a type of white blood cell that limits harmful immune responses, such as negative responses against transplanted cells. Clinical trials suggest Treg therapy is safe, but its effectiveness is limited by the fact that each Treg cell is slightly different, which means only a small number will fulfil the desired function. Our lab has created Tregs that have been altered to detect a protein found on the donor transplanted cells, but not the recipient's cells; this helps "attract" the Tregs to the site of the transplant, allowing for a better, more targeted response. My project aims to further enhance this approach by using only the most suppressive Tregs. I will genetically engineer Tregs so that only those that express a protein known as Helios will be redirected towards transplants. Helios-expressing Tregs are more suppressive than Tregs that lack Helios expression. In fact, loss of Helios is associated with destabilized Tregs, which pose a safety concern for cell therapy. Overall, my research aims to improve the safety and protective function of Treg cell therapy for islet transplantation. This work can provide better treatment options to over 300,000 Canadians living with T1D, and can further improve outcomes for other cases of autoimmunity and transplantation.