https://medicalxpress.com/news/2023-12-salty-immune-cells-brain-linked.html

Researchers still sought the source of the IL-17 acting on the brain macrophages. Based on their previous work, the researchers’ initial hypothesis was that the gut releases IL-17, which then travels to the brain through the bloodstream. Once there, it sets off a reaction that damages the ability of brain blood vessels to respond appropriately to increased brain activity. However, blocking the brain blood vessels’ ability to respond to IL-17 only partially rescued cognitive impairment, suggesting that there was another source of IL-17 acting on the brain.

One clue came from other recent studies suggesting that one layer of the protective covering of the brain, known as dura mater, contains immune T cells that can both secrete IL-17 and affect the behavior of mice. Using special mice where cells light up fluorescent green when they make IL-17, the researchers confirmed that hypertension increases IL-17 in the dura mater, which is then released into the tissue.

Normally, barriers exist within the protective covering of the brain, called the meninges, to prevent unwanted spillage into the brain. However, this barrier appeared to be disrupted in the mice with experimentally induced hypertension, and this disruption allowed IL-17 to enter the cerebral spinal fluid.

Two additional experiments helped to confirm this hypothesis. First, a drug was used to prevent T-cell movement from the lymph nodes into the meninges. Second, an antibody was used to block the activity of T cells in the meninges. In both cases, cognitive function was restored in the mice with hypertension, suggesting that targeting overactive T cells could be a new treatment approach worth exploring.

“Together, our data suggest two different effects are caused by hypertension,” said Dr. Iadecola. “One is IL-17 acting on blood vessels, but this appears to be relatively minor. A more prominent central effect is caused by cells in the meninges releasing IL-17 which directly affects immune cells in the brain. It is these immune cells, activated by signaling from the meninges, that ultimately affect the brain in a way that causes cognitive impairment.”

Dr. Iadecola and his team are now looking to connect the dots between the activation of immune cells in the meninges and decreased cognitive function.

Previous work by the group suggested a connection between a high salt diet which suppressed the production of the chemical nitric oxide in brain vessels that in turn led to buildup of tau, a toxic protein that forms clumps in neurons affected by Alzheimer’s disease.

The present findings also show suppression of nitric oxide production within brain vessels, and whether this also leads to an increase in tau production is currently under investigation.