Multiple sclerosis (MS) affects approximately 2.5 million people worldwide. While the disease is known to be caused by immune cells that attack myelin, how these immune cells penetrate the blood-brain barrier to cause such damage was unknown. Researchers at the University of California, Irvine have now uncovered two distinct ways that immune cells gain access neurons. Their findings were reported yesterday in the journal Cell Reports.
The researchers wanted to discover how Th1 and Th17 cells, the lymphocytes known to be involved in degrading myelin in MS, gain access to neurons. They used a mouse model with experimental autoimmune encephalomyelitis, a mouse version of MS.
They genetically labeled endothelial cell tight junctions in blood vessels with fluorescent protein to study how these junctions are involved in multiple sclerosis. They observed that the tight junctions became deteriorated in the presence of Th17 cells early in the disease’s progress. Three days later, Th1 cells were found to be degrading myelin and neurons even though they did not pass the tight junctions like Th17 cells. The Th1 cells instead accessed neurons through the caveolae, specialized cell membranes located on blood vessels. Mice bred to lack caveolae were found to have almost no Th1 in the brain and spinal cord.
These findings indicate that drugs to treat multiple sclerosis should target these two pathways to slow progression of the disease.