Grant: Project Grant

Multiple Sclerosis (MS) is a chronic inflammatory disease of brain and spinal cord affecting up to 1/500 people in Canada. It causes substantial disability in young adults and results in considerable emotional, physical, social and economic burden on the patients 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. Oligodendrocytes are myelin-producing cells which support and insulate neurons. In MS they are injured by the inflammatory immune cells, leaving neurons vulnerable. This leads to neurological deficits that can be reversible if the oligodendrocytes can recover sufficiently, but this is often not the case. Immune cells called pro-inflammatory T cells are considered to orchestrate neuroinflammation in MS and its animal model experimental autoimmune encephalomyelitis (EAE), but whether they can directly injure oligodendrocytes remains undefined. Using live imaging, we have recently shown that T cells can directly contact oligodendrocytes in the brain/spinal cord of EAE animals, and we also found T cells juxtaposed with oligodendrocytes in human MS brain tissue. We now want to characterize which molecules are implicated and what are the consequences of these direct T cell-oligodendrocytes interactions. As preventing immune-mediated oligodendrocyte damage could decrease the accumulation of neurological disability in MS, we will moreover test if targeting the contact molecules identified could represent a future treatment avenue to protect the cells of the brain and spinal cord in MS.