The blood-brain barrier (BBB) was highlighted in a session at the #MSParis2017 conference where researchers presented their recent findings on the relationship between the BBB and MS. The BBB is a network of cells (called endothelial cells) that line all the blood vessels in the brain. These cells are so tightly connected that they prevent harmful substances such as bacteria and toxins from entering the brain and spinal cord (collectively called the central nervous system or CNS). In MS, the BBB is compromised and becomes leaky, allowing white blood cells from the immune system to pass through the barrier and enter the CNS. The white blood cells then attack myelin (the coating around the nerve cells in the CNS) which results in inflammation and lesions. Many research teams are examining what causes the BBB to weaken and ways to prevent this from happening.
Dr. Alexandre Prat: DICAM is a novel molecule that promotes the migration of harmful immune cells to the brain and spinal cord
MS Society funded researcher, Dr. Alexandre Prat from Centre de Recherche du Centre Hospitalier de l’Université de Montréal, talked about the factors that may regulate the movement of white blood cells from the blood to the CNS. One of these factors is the presence of cell adhesion molecules (CAMs) which are proteins found on the surface of immune cells that enable them to adhere to and cross over the BBB. Dr. Prat and his research team have discovered a specific CAM, called DICAM, that may assist in orchestrating immune cells to accomplish this invasion. DICAM was found in the tissues of people with RRMS and is associated with the production of pro-inflammatory factors on white blood cells. Furthermore, Dr. Prat showed that reducing the quantity of DICAM prevented the migration of harmful immune cells into the CNS and hence delayed the onset of disease in a mouse model of MS. The data presented by Dr. Prat identified DICAM –a novel molecule that is found on white blood cells that promotes their migration across the BBB and into the CNS, where they cause damage.
Elizabeth Gowing: integrin α8 is a protein that is involved in facilitating the migration of immune cells into the central nervous system.
We also heard from Elizabeth Gowing – a PhD student in Dr. Alexandre Prat’s lab and the recipient of an MS Society PhD studentship award. Her research looks at proteins called integrins which facilitate the migration of cells across the BBB. She discovered a specific integrin, called integrin α8 is involved in several ways. Gowing’s work shows integrin α8 (1) is linked to an increased quantity in pro-inflammatory immune cells, (2) is found in active MS lesions in the CNS, and (3) blocking integrin α8 decreases the migration of harmful immune cells into the CNS of mice that have MS like disease.
A member of my team also had a chance to talk to Elizabeth Gowing at the conference to find out a bit about what motivated her to get involved in research in MS and more about her project. Here is their conversation (8:14 minutes):
Catherine Larochelle: epidermal growth factor-like protein 7 (EGFL7) is a novel protein player that limits the infiltration of pro-inflammatory immune cells in MS
Following in the footsteps of her doctoral supervisor, Dr. Alexandre Prat, Dr. Catherine Larochelle, now a scientist at the Université de Montréal, examined the role of epidermal growth factor-like protein 7 (EGFL7) in regulating the migration of immune cells in MS. EGFL7 was previously demonstrated to enhance endothelial cell (cells lining the BBB) survival under stressful conditions. Dr. Larochelle discovered that EGFL7 can limit the amount of CNS infiltration of pro-inflammatory immune cells into the CNS by promoting BBB integrity and securing activated immune cells to the perivascular space (space that spans between blood vessels and brain matter) to prevent their migration into the CNS. Therefore, Dr. Larochelle believes that EGFL7 could represent a new therapeutic target in MS.
The studies presented at this session are important steps to finding out more about the BBB so that future studies can focus on how the BBB can be strengthened to prevent immune cells from entering the CNS, ultimately putting a halt on progression.
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