Interleukin-17A (IL-17A), a molecule that mediates immune and inflammatory responses, likely promotes inflammation and tissue damage in relapsing-remitting multiple sclerosis (RRMS) and should be considered a potential target for treating the disease, a study reports.
The findings of the study, “IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis,” were published in the Journal of Neuroimmunology.
Previous studies have shown that IL-17 is produced by certain immune cells and nerve cells at active brain lesions in the central nervous system (CNS; composed of the brain and spinal cord), where its effects, combined with those of other pro-inflammatory molecules, cause inflammation and tissue damage.
It is also known that IL-17 can disrupt the integrity of the blood-brain barrier (BBB), a highly selective and semipermeable barrier that protects the brain from possible insults (like viruses) carried in the blood. It does so by interfering with cells that line the walls of small blood vessels (endothelial cells) and which are a point of contact between the brain and the body.
Studies in mouse models have also shown that lowering brain levels of IL-17A, through specific drugs or genetic manipulation, may slow the deterioration of the BBB and some symptoms of experimental autoimmune encephalomyelitis (EAE) in animal models of multiple sclerosis. EAE mimics key features of MS in humans.
Now, researchers from Genentech, a subsidiary of Roche, in collaboration with investigators from the Weill Institute for Neurosciences, set out to explore the mechanisms by which IL-17 compromises BBB integrity, and leads to the development of EAE in mice.
First, researchers showed that treating animals with an anti-IL-17A antibody reduced disease activity in mice with EAE. However, treatment with an anti-IL-17F antibody that targeted IL-17F, another member of the IL-17 family that shares many similarities with IL-17A, did not have any effect.
Then, the team analyzed cerebrospinal fluid (CSF) samples from 50 RRMS patients, and found their levels of IL-17A abnormally high compared to healthy individuals serving as controls. Of note, CSF is the liquid that circulates in the brain and spinal cord.
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