Antigen-presenting cells (APCs) account for a significant proportion of the cells found within lesions of multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). These APCs have the ability to capture myelin debris and to promote either an inflammatory response or either a tolerogenic response from the effector lymphocytes. I intend to understand the molecular mechanisms which govern the switch between these two opposite type of immune responses. This project will focus on the Wnt signalling pathway since previous studies have shown that an activation of this pathway on APCs could lead to a reduced inflammation in the gut. I will first demonstrate that during brain infiltrating APCs express higher levels of Wnt receptors. Secondly, I will demonstrate that activation of this pathway on APCs leads to an anti-inflammatory profile from the APCs, which induce a tolerogenic response from effector lymphocytes. Finally, I will demonstrate that activation of the Wnt pathway in APCs leads to reduced EAE disease. This study aims to demonstrate that activation of the Wnt pathway on APCs favors the induction of an anti-inflammatory response, and will help in the development of strategies to design new therapies in the treatment of autoimmune diseases, such as MS.
|Effective start/end date||7/1/14 → 6/30/17|
- National Multiple Sclerosis Society (FG 2065-A-1)
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