Le rôle de l'intégrine alpha8 en la sclérose en plaques

 

Elizabeth Gowing

Centre de recherche du CHUM

 

Domaine : Neurosciences, santé mentale et toxicomanies

Programme : Formation de doctorat

Concours 2016-2017

Partenaire:

Société canadienne de la sclérose en plaques

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) affecting over 100,000 Canadians. MS activity is a result of self-targeting immune cells that migrate across the brain and spinal cord blood vessels into the CNS. Cell adhesion molecules (CAMs) on immune cells facilitate this process. This leads to destruction of myelin, the fatty insulation around nerve cells, which causes many neurological symptoms and renders the nerve cells vulnerable to damage. The secondary progressive stage of MS relates to on-going degeneration of nerve cells in the brain and spinal cord. This is thought to be a result of long-lived immune burden and demyelination. Thus, identifying novel targets to specifically prevent autoimmune cells from entering the CNS is a major therapeutic goal.

Early therapeutic interventions that prevent damage to the nerve cells and myelin can potentially delay or prevent progression altogether, of which currently there is no cure. TH17 cells are thought to be the disease initiating immune cells in MS. Our lab has identified the expression of a novel CAM, integrin alpha8, on this immune cell subset. The binding partner of integrin alpha8, nephronectin, is found on CNS blood vessels, suggesting that the interactions between these proteins may promote migration of TH17 cells from the blood into the brain and spinal cord. I propose to use a variety of cell culture techniques, using healthy donor and MS patient tissue, and animal models of MS to investigate the role of integrin alpha8 in neuroinflammatory disease.

My hypothesis is that integrin alpha8 is primarily expressed by autoimmune cells and that by binding nephronectin, alpha8 facilitates early entry of these cells into the brain and spinal cord, leading to MS relapses. Blockade of this integrin may prove to be a beneficial therapeutic approach for the treatment of MS.