Immune Cells Cross Blood-Brain Barrier, Promote Multiple Sclerosis
Cell structure may allow immune cells to attack myelin in multiple sclerosis.
New findings from a study published by Cell Reports suggest that immune cells may attack neurons in multiple sclerosis (MS) by crossing the blood-brain barrier. The study authors wrote that novel therapies should focus on inhibiting demyelination from rogue immune cells.
The loss of myelin results in the diminished cognitive and physical function that is characteristic of MS. While not all patients with MS experience the same symptoms, the rate of demyelination is directly correlated to worsening of the disease.
It is known that immune cells launch an attack against neurons, but much is currently unknown about how the cells are able to break through the blood-brain barrier, which is a notoriously difficult task.
Previously, researchers uncovered that Th1 and Th17 lymphocytes are involved with MS-related demyelination; however, it was unclear how the cells cross the blood-brain barrier.
The blood-brain barrier refers to blood vessels that protect the brain and the spine against chemicals, microbes, and other cells. The barrier is difficult to penetrate because the endothelial cells that compose the vessels are tightly bound together, according to the authors.
“In autoimmune diseases like multiple sclerosis, immune cells that enter the brain and spinal cord cause disease,” said lead author Sarah Lutz, PhD. “A better understanding of how these cells cross the blood-brain barrier will aid our efforts to develop specific therapies to keep them out.”
In the study, the authors examined how Th1 and Th17 lymphocytes affected neurons in mice models of MS by fluorescently labeling blood vessel endothelial cell tight junctions.
The authors discovered that the tight junctions were observed to deteriorate in the presence of Th17 cells, according to the study. The authors noted that deterioration took place early in the disease.
After 3 days, the researchers discovered that Th1 lymphocytes significantly degraded myelin and neurons, but did so in a different manner than Th17 cells, according to the study.
Instead of hijacking endothelial cell tight junctions, Th1 lymphocytes gained access to neurons by passing through the endothelial cells using caveolae, which are specialized cell membrane structures on the surface of cells that help molecules and cells pass into or through cells, according to the authors.
In mice models of MS bred to lack caveolae, the authors discovered almost no Th1 lymphocytes in the brain and spinal cord. These findings suggest that caveolae on endothelial cells are necessary to help transport Th1 cells through the blood-brain barrier, according to the study.
While additional studies are needed, investigational drugs should be created to prevent caveloae from transporting immune cells across the blood-brain barrier in MS.
“This is the first time we have ever seen, in live animals in real-time, the different means by which these 2 cell types gain access to myelin and nerves,” Dr Lutz said. “Now that we know how these cells get to neurons, drugs or small molecules can be designed that interfere with or block each of these processes to help treat and possibly prevent multiple sclerosis.”