How Rogue Immune Cells Cross the Blood-Brain Barrier to Cause Multiple Sclerosis
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.
In multiple sclerosis, 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 led by Sarah Lutz, University of Illinois at Chicago College of Medicine while she was a post-doctoral fellow of Dritan Agalliu at Columbia University; and Sunil Gandhi, University of California, Irvine, have uncovered two different ways immune cells gain access to neurons and wreak their havoc.
Multiple sclerosis is a neurodegenerative inflammatory disease that affects approximately 2.5 million people worldwide. Immune cells turn against the body and cause damage to the myelin sheath, which encases neurons like the insulation on a wire. Loss of myelin interferes with the transmission of signals along the nerve fibers and impairs motor function, including walking and speech. Symptoms, which can be sporadic or progressive, range from mild to debilitating.
While researchers have known that two different kinds of immune cells, Th1 and Th17 lymphocytes, are involved in degrading myelin around neurons in multiple sclerosis, they didn’t know exactly how these cells crossed the blood-brain barrier to access neurons.
The blood-brain barrier is a bit of a misnomer. It 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.
“In autoimmune diseases like multiple sclerosis, immune cells that enter the brain and spinal cord cause disease,” said Lutz, assistant professor of anatomy and cell biology in the UIC College of Medicine and the lead author of the paper. “A better understanding of how these cells cross the blood-brain barrier will aid our efforts to develop specific therapies to keep them out.”
To explore how Th1 and Th17 immune cells gain access to neurons in multiple sclerosis, Lutz and her colleagues looked at the blood-brain barrier in mice with experimental autoimmune encephalomyelitis — a mouse version of multiple sclerosis.