Grant: Project Grant

Multiple Sclerosis (MS) is a chronic inflammatory disease of brain and spinal cord affecting up to 1/400 people in Canada. It causes substantial disability that does not respond well to treatments in the chronic progressive phase, and therefore results in considerable emotional, physical, social and economic burden on the person and their relatives. While the exact cause of MS is still unknown, we know that there is an aberrant response of immune cells against cells of the brain and spinal cord in MS. Immune cells called pro-inflammatory T cells are considered to orchestrate neuroinflammation in the early phases in MS and its animal model experimental autoimmune encephalomyelitis (EAE), but their role in the chronic progressive phase of the disease remains undefined. Moreover, in progressive MS the immune cells of the brain and spinal cord play a detrimental role in contributing to slow expansion of lesions and damage. Using live imaging, we have recently shown that T cells can directly contact CNS cells in MS and EAE through 'glue' molecules called cell adhesion molecules. We now want to characterize how infiltrating peripheral immune T cells use a specific cell adhesion molecule to interact with immune cells of the brain and spinal cord, what are the consequences of these interactions, and whether we can target this cell adhesion molecule to decrease the chronic inflammation and accumulation of disability. If targeting the contact molecule identified limits inflammation and progression in the animal model of MS, it could represent a future treatment avenue to ameliorate the progression of disability in MS.