Grant: Doctoral: Vanier Canada Graduate Scholarships

In autoimmune disease, the immune system that is designed to prevent infection and cancer attacks the healthy body. There are over 60 types of autoimmune disease - examples include type 1 diabetes and inflammatory bowel disease. Autoimmune disease is a significant economic and psycho-social burden and an enormous challenge clinically, as treatment is symptomatic but not yet curative. One promising solution is immunomodulation, whereby the immune system is "reprogrammed" to suppress unwanted inflammation. Regulatory T cells (Tregs) are potent contributors in suppressing inflammation and can directly restrain inflammation in a manner that targets specific antigens, or molecules that are causative to inflammatory disease. Human skin is particularly rich in Tregs. I propose to harness the skin immune system to direct immunosuppressive Treg responses using a technique called topical immunomodulation. My doctoral thesis will examine how to 1) expand skin Treg populations, 2) assess their function in targeted immunosuppression, and 3) re-home skin Treg into organs affected by inflammation. I will investigate the capacity of ultraviolet B radiation, topical corticosteroid and topical vitamin D in expanding functional Treg. Topical vitamin A will be examined for its potential in re-homing immunosuppressive Tregs into intestinal tissue. I will use mouse models of allergic contact dermatitis, type 1 diabetes, and inflammatory bowel disease to test the effectiveness of these topical immunomodulatory strategies in treating or curing inflammation in mice. In humans, my doctoral work will test whether topical corticosteroid and/or vitamin D ointments can expand functional Treg in the skin and blood of people with nickel or pollen allergies. The findings of my doctoral work will contribute critically essential knowledge for the development of clinically effective therapy for patients with autoimmune disease and related inflammatory disorders.