Immune cells that destroy myelin in multiple sclerosis (MS) access the brain and spinal cord via two different routes, a new mouse study shows. This suggests that therapies which target these entry routes may shield the brains of MS patients from further damage.
The study, “Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation,” appeared in the journal Cell Reports.
MS symptoms arise when immune cells — mainly Th1 and Th17 lymphocytes — attack the myelin sheath that protects neurons. While these cells have long been known to destroy myelin, no one knows how they penetrate the blood-brain barrier and access the brain.
The blood-brain barrier — blood vessels with a highly specialized layer of endothelial cells tightly glued together by complexes called tight junctions — protects not only the brain but also the spine from getting into contact with potentially harmful chemicals, microbes and even cells that circulate in the blood.
“In autoimmune diseases like multiple sclerosis, immune cells that enter the brain and spinal cord cause disease,” Sarah Lutz, the study’s co-lead author, said in a news release. “A better understanding of how these cells cross the blood-brain barrier will aid our efforts to develop specific therapies to keep them out.”
Along with other researchers, Lutz, an assistant professor of anatomy and cell biology at the University of Illinois at Chicago College of Medicine, used a mouse model of human MS — the so-called experimental autoimmune encephalomyelitis (EAE) model — to investigate how Th1 and Th17 immune cells gain access to neurons.
These mice, as well as healthy control mice, were made to express a fluorescent protein of the endothelial cells present in tight junctions. Researchers performed imaging of this protein in real-time.
Their analysis showed that in the presence of Th17 cells, the tight junctions that keep the blood-brain barrier whole were severely damaged in EAE mice. This deterioration also happened early in the disease course.
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