Loopholes for lymphocytes
Multiple sclerosis is a neurodegenerative disease with an unknown etiology, in which cells of the immune system damage the myelin sheath of the processes of neurons. This is accompanied by a decrease in their resistance to environmental factors, a deterioration in the speed and quality of pulse transmission through them. Clinically, this is expressed in disorders of sensory and motor functions, cognitive disorders. According to statistics, 2.5 million people worldwide suffer from multiple sclerosis.
It is known that two types of T helper lymphocytes have a damaging effect on myelin in multiple sclerosis: Th1 and Th17. It is still unclear how these cells penetrate the blood-brain barrier (BBB) and get from the vessel into the brain tissue. Researchers from the University of Illinois led by Sarah Lutz and the University of California led by Sunil Gandhi have discovered two mechanisms for overcoming BBB by immune cells.
The blood-brain barrier (BBB) is a structure that prevents the penetration of toxins, bacteria, inflammatory cells circulating in the blood and other damaging factors from the blood into the brain and thus protects the central nervous system. The basis of BBB is made up of vascular walls, which are practically impenetrable due to protein complexes ("tight contacts") that firmly bind endothelial cells that line the vessels from the inside. Blood vessels of other organs are more permeable due to less strong connection between endothelial cells. This allows the exchange of molecules and cells from the blood to the tissues and back.
To study the mechanism of penetration of Th1 and Th17 lymphocytes into the brain, researchers conducted an experiment on mice with induced autoimmune encephalitis – an analog of multiple sclerosis in humans. Mice were genetically modified to mark the tight contacts that hold endothelial cells together with a fluorescent protein to check whether they are involved in the process of autoimmune damage to nervous tissue.
The researchers noted that in the presence of Th17 lymphocytes, tight contacts were significantly weakened, and this happened at the very beginning of the disease. Thus, Th17 overcome BBB through protein bridges that bind endothelial cells.
Approximately on the third day of the experiment, Th1 lymphocytes were detected in the brain tissue, and the destruction of myelin began. But unlike Th17 lymphocytes, Th1 lymphocytes got into the brain without damaging tight contacts: endothelial cell membrane structures, the so-called caveoles, were involved.
Caveoli (from Lat. "small caves") exist on the surface of different types of cells and provide passage of molecules into or through the cell. In mice with autoimmune encephalitis, in which caveoles were absent after gene modification, Th1 lymphocytes were not found in the spinal cord and brain tissue. Thus, it was concluded that the primary role of caveolus endothelial cells in overcoming BBB by Th1 lymphocytes.
The results obtained in this study should help to develop a new approach in the treatment of multiple sclerosis based on blocking each of the two described processes of lymphocyte penetration through the BBB.
Article by Sarah E. Lutz et al. Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation published in the journal Cell Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of UIC Today: How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis.