A new study suggests drug designers working on therapies against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons. Using a mouse model of MS, they found that Th17 immune cells acted on the blood-brain barrier, while Th1 cells entered the brain through more specialized structures.
 
In MS, immune cells degrade the insulation that protects neurons and allows them to signal to one another, but little is known about how immune cells penetrate the blood-brain barrier to get to neurons. Researchers at the University of Illinois at Chicago College of Medicine uncovered two different ways immune cells gain access to neurons and wreak their havoc.
 
The blood-brain barrier not only protects the brain, but also the spine, and refers to the fact that blood vessels that supply the brain and spine are virtually impermeable because the cells that make up those blood vessels – called endothelial cells – are bolted tightly together by protein complexes called tight junctions. This prevents certain chemicals, harmful microbes, and cells that circulate in the blood from gaining access to the brain and spine. In blood vessels that supply other organs of the body, endothelial cells are more loosely bound to one another and the connections can be adjusted to allow for the exchange of molecules and cells from the bloodstream into tissues and vice versa.
 
While researchers have known that two different kinds of immune cells, Th1 and Th17 lymphocytes, are involved in degrading myelin around neurons in MS, they didn't know exactly how these cells crossed the blood-brain barrier to access neurons. To explore how Th1 and Th17 immune cells gain access to neurons in MS, the researchers looked at the blood-brain barrier in mice with a mouse version of MS. They genetically labeled blood vessel endothelial cell tight junctions to examine if and how tight junctions are involved in mice. The researchers found that the tight junctions were significantly deteriorated in the presence of Th17 cells, and that this took place early in the onset of disease.
 
Approximately three days later in the disease process, they found that Th1 cells were accessing and degrading myelin and neurons by going through the blood vessel endothelial cells using specialized cell membrane structures called caveolae. Caveolae are small pits or "caves" found on the surface of many cell types and help facilitate the passage of various molecules and cells into and/or through cells. In mice with mouse model MS bred to lack caveolae, the researchers found almost no Th1 cells in the brain and spinal cord. They determined that caveolae on endothelial cells that make up blood vessels are required to help ferry Th1 cells through the blood-brain barrier.
 
The findings were published in the journal Cell Reports.