Discovering how immune cells get into the brain in MS

The brain is one of the most highly protected organs in the human body. Not only does it have a hard bony protective layer, the skull; it also has what is known as the blood brain barrier. This barrier selectively allows certain things into the brain, while preventing others from entering.

The barrier is made up of cells called epithelial cells. These cells are wedged extremely close to each other and form what are called tight junctions – bridge-like structures between the cells that prevent anything slipping through between them. Special receptors and gateways on the cell surfaces allow certain things past – for example, passing nutrients to the brain and removing waste products from the brain.

In MS, it is thought that there is a disruption to this barrier that allows immune cells into the brain. These immune cells then attack the protective myelin covering nerve cells, leading to MS symptoms. Stopping immune cells from passing through the blood brain barrier could be a way of treating MS – indeed, one MS treatment, natalizumab (Tysabri), acts in this way.

It is known that two different kinds of immune cells, Th1 and Th17 cells, are important in the attack on myelin in MS. But one part of the puzzle in MS is what regulates the entry of these immune cells into the brain in the first place.

Research led by Sarah Lutz, at Chicago College of Medicine, University of Illinois, has now shown that these two different types of immune cells get in to the brain by two different routes.

Important mechanism

In this study, published in the journal Cell, the scientists looked at animals with illnesses similar to MS. In these animals, the scientists made one of the proteins that is involved in the tight junctions fluorescent in order to make them visible under the microscope. They found that, at the onset of the disease, the tight junctions broke down, allowing the Th17 cells to get into the brain.

A couple of days following this, the Th1 immune cells started entering the brain, but these were entering through a different mechanism. These cells entered using a special gateway on the cells called caveolae. These are like a very small “caving in” of the cell membrane to form a pocket or parcel that moves across the cell and into the brain. This mechanism is normally used for the transport of various signals through the blood brain barrier, but appear to be hijacked by the Th1 cells.

When the researchers looked at animals that had a genetic mutation in a protein called caveolin, which helps forms the little parcels, they found that the Th1 cells were prevented from getting in to the brain and spinal cord. This confirmed that this mechanism is vital to help transport Th1 cells through the blood-brain barrier.

This study highlights the mechanism by which some of the immune cells get ferried across the blood brain barrier, allowing them to attack and damage the myelin coating on nerve cells. While this is an early fundamental scientific study, it suggests that this could be a very good mechanism for scientists to target to prevent the attacks of MS.

With thanks to MS Research Australia – the lead provider of research summaries on our website.