Study: Interrupting immune response improves MS outcomes

April 01, 2022
A human immune system is a complicated system of interacting parts. Proteins trigger other proteins to activate immune cells and direct them toward germs. But if those proteins mistakenly direct immune cells toward healthy tissue, autoimmune diseases such as multiple sclerosis — which attacks neurons — can arise.

A new study by researchers at the West Virginia University School of Medicine suggests part of the immune system shows promise as a potential target for MS therapies. The study focused on STAT5, one of the many proteins circulating in the body that can metaphorically turn genes on or off.

The infiltration of immune cells into the meninges is a hallmark of MS. The meninges are a series of three membranes that surround the central nervous system. They act as a checkpoint, regulating the migration of cells into the brain or spinal cord. Researchers wanted to know if STAT5 tetramers played a role in signaling white blood cells to interact and move through the meninges. If they did play such a role, the researchers wanted to learn more about it. In particular, researchers wanted to investigate the molecular chain of events that might cause STAT5 tetramers to command another protein — CCL17 — to tell T cells to attack the central nervous system through “friendly fire.”

The research team used two groups of mice to explore this topic. The first group had been genetically modified so its STAT5 tetramer proteins could not rearrange themselves in ways that would trigger the problematic CCL17 response. The second group was genetically normal. The researchers injected both groups of mice with myelin-reactive T cells to induce an experimental form of MS called experimental autoimmune encephalomyelitis, or EAE.

In response, the genetically-normal mice developed EAE in the conventional way, but the genetically modified mice didn’t. Interrupting their STAT5 tetramer “chain reaction” protected them against the disease. Not only did the genetically modified mice display milder and delayed paralysis, but a later examination of their spinal cords revealed healthier nerves that were better at transducing signals.

The results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers argue insights such as the ones gleaned from this study can point to future treatments for MS.

The findings appear in the Proceedings of the National Academy of Science.

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