The Natural Killer Nerve Cells That May Pave The Way To Removing Neuropathy

Today's fascinating post from sciencemission.com (see link below) is one of those rare beasts in that extremely complex science is brought to the average reader in such a way that it seems almost understandable. Basically, it looks at how neuropathy symptoms come about and at how, with a few adjustments, the immune system can remove the damaged axons that cause nerve pain and allow new ones to grow in their place. The article does point out that it's extremely risky to tinker with the immune system; so we're a long way off effective treatments in humans but the theory is fascinating. We suffer neuropathy symptoms because our axons are damaged but not destroyed, so they keep sending pain signals to the brain to remind us of that damage. However, by increasing the number of NK cells (interestingly called 'Natural Killer' cells), we should be able to remove the damaged material completely, to allow new, healthy cells to grow in their place. You need to read the article to see how this may be possible but it's well worth a read, if only to learn a little more about how neuropathy works and how our immune system is almost magical in how it operates. Once again, kudos to all lab rats who's sacrifice makes humans live healthier lives!!

Role of immune cells in relieving pain after peripheral neuropathy
Added January 31st 2019, Author: newseditor

In animal models of a totally crushed peripheral nerve, the damaged axons are broken down, allowing healthy ones to regrow. But humans rarely suffer complete axonal damage. Instead, axons tend to be partially damaged, causing neuropathic pain -- a difficult-to-treat, chronic pain associated with nerve trauma, chemotherapy and diabetes. A new study in Cell, explores the role of immune cells in breaking down damaged nerves. The findings may change our understanding of neuropathic pain and how to treat it.

Early in their work, researchers noticed that immune cells called natural killer (NK) cells would strip away the axons of neurons in a petri dish. NK cells are part of our body's rapid, innate immune response to threats such as viruses and cancer.

The team then started growing sensory neurons in a petri dish. They noticed these dissociated neurons began expressing large amounts of RAE1, a protein that invites NK cells to attack. When these neurons were co-cultured with activated NK cells, the NK cells began breaking down the injured nerves.

"We found that the natural killer cells would eat away at the axons of the neurons, but wouldn't destroy their cell bodies," says the co-senior author. "This which was exciting as it allowed for the possibility that new, healthy axons could grow from them."

The team then looked to see whether these results held up in a living animal. They increased the function of NK cells in mice and then partially crushed their sciatic nerve, the main nerve that runs down the back of the leg. Then they waited and watched.

"It was as if the neurons knew what happened," says the co-senior author. "They started to express the receptors that leave them susceptible to a natural killer cell attack. And the natural killer cells were responding, coming into the nerve and clearing those damaged axons."

Within days after the nerve crush, tests indicated that the immune-stimulated mice had significantly reduced sensation in the affected paw. But once the damaged axons were cleared, healthy ones began to grow back in their place. At around two weeks after the crush, the mice's paws regained sensation.

Other mice, whose NK function wasn't enhanced, had a similar recovery timeline. But because their partially damaged axons hadn't been cleared away as efficiently, tests continued to show high levels of touch-induced pain 30 days or more after the injury. This scenario is analogous to human neuropathic pain, in which damaged nerves that aren't fully broken down may continue sending pain signals to the brain, causing chronic pain and hypersensitivity.

Interfering with the immune system always carries risk, but the team's work suggests that finding a way to modulate NK cell function could perhaps clear out damaged axons, allowing healthy axonal regrowth and potentially decreasing chronic neuropathic pain. Ultimately, understanding more about the role of NK cells in selective axonal degeneration will lead to a greater understanding of the mechanisms behind neuropathic pain. And with greater understanding, better treatments will follow.

https://www.cell.com/cell/fulltext/S0092-8674(18)31636-2

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fnatural-killer-cells_2&filter=22&redirected=1

Edited January 31st 2019

http://sciencemission.com/site/index.php?page=news&type=view&id=health-science%2Frole-of-immune-cells-in