Using a mouse model of human multiple sclerosis (MS), scientists have discovered how T-cells can easily damage the brain.
Inflammatory T-cells in MS are a key group of cells found in the immune system. The T-cells cross the blood-brain barrier in order to penetrate the brain and attack the central nervous system.
Researchers have continuously tried to decipher this mechanism in order to develop new medications and to address this particular step in the disease’s development.
Scientists conducting the “EB12 is highly expressed in multiple sclerosis lesions and promotes early CNS migration of encephalitogenic CD4 T-cells” study have discovered a protein on the surface of T-cells, called EB12, which is essential to penetration. EB12, also known as GPR183 (Epstein-Barr virus-induced G protein-coupled receptor 2) works as a receptor for another protein, a ligand known as 7a,25-dihydroxycholestrol.
The scientists from Germany’s Mainz University Medical Centre found that EB12 expression in T-cells facilitates their entry in the brain. With increasing concentrations of EB12 and its ligand, more T-cells penetrate the blood-brain barrier, resulting in damage to the brain.
They also found that cells expressing higher concentrations of EB12 accumulated in inflamed brain areas of MS patients.
Florian Wanke said: “This data allowed us to conclude that in humans, the receptor and an elevated ligand concentration promote infiltration by T-cells and thus the development of CNS-disease.”
The team used an established animal model for the study of MS, to discover the effects of EB12. They began by observing that ligand production, via a class of protein called enzymes, peaks in the CNS during inflammation.
“The more of these enzymes are active, the greater the number of ligands that are able to channel T-cells across the blood-brain barrier,” explained Florian Kurschus, the study’s lead author. “So we were able to conclude how actually increased ligand is produced in the inflamed CNS tissue.”
There are a number of therapeutics already in existence, which belong to the same class of receptors as EB12. Kurschus said: “We already have plans to explore their efficacy in future experiments.”
Source: MS-UK (21/03/17)