Molecular mechanisms underlying T cell/oligodendrocyte interactions as target for neuroprotective strategies in MS
Principal Investigator: Dr. Catherine Larochelle
Affiliation: Université de Montréal
Year awarded: 2018-2019
Amount Awarded: $367,000
Keywords: Myelin, Oligodendrocyte, Th17, immune-oligodendrocyte interactions
- Myelin, the covering on the nerve fibers destroyed by immune cells in multiple sclerosis (MS), is provided by cells in the brain and spinal cord called oligodendrocytes.
- The interactions between immune cells and oligodendrocytes are unknown and there is a need to better understand this interaction.
- The research team will:
- Identify molecules that allow the interaction of a subset of white blood cells and oligodendrocytes in inflammatory conditions
- Block the immune-oligodendrocyte interactions to prevent the destruction of myelin
Pro-inflammatory immune cells called Th17 cells are harmful to MS. They express specific ‘cell adhesion molecules’, which are molecules that they use to talk with and stick to other cells. Recent research demonstrated that Th17 cells, entering the brain, can directly cause damage to oligodendrocytes (cells responsible for providing a myelin sheath around the neurons) and can impair the processes of myelin reparation by sticking to them. Dr. Catherine Larochelle and her research team plan to demonstrate 1) that the oligodendrocytes are expressing the specific complementary binding site of the ‘cell adhesion molecules’ expressed by the Th17 cells, and especially in inflammatory conditions; 2) that blocking these adhesion molecules or their binding site can protect the oligodendrocytes and their myelin sheath from Th17; 3) that in an animal model of MS, removing the Th17 cells that express these ‘cell adhesion molecules’ or by deleting the ligand on the oligodendrocytes results in an improved course of MS-like disease.
Potential Impact: Identify molecules that could become treatment targets to limit the damage to the cells of the brain and spinal cord and restore good conditions to accelerate repair and decrease progression in MS.
Project Status: In Progress