Picky protein behind inflammation offers new target for MS treatments

With no cure and treatments that focus primarily on managing symptoms and slowing progression of the disease, there is a dire need for new therapies to tackle multiple sclerosis (MS). Scientists have just made a promising discovery through experiments on mice which could help things along, by demonstrating how neutralizing a specific protein can selectively temper the inflammation that drives the disease, which makes it an ideal target in the ongoing pursuit of a cure.

MS is an autoimmune disease in which the body's immune system mistakenly attacks the protective layer around the nerves in the brain and spinal cord called the myelin sheath. This causes inflammation that in turn disrupts the electrical signals traveling from the brain to the rest of the body which leads to all kinds of symptoms, ranging from muscle spasms to mobility issues to a loss of vision.

It is this inflammation that is the focus of new research from a team led by scientists at the University of California, Irvine (UCI), who investigated how regulatory T cells called Tregs might have an important role to play. These cells specialize in suppressing immune responses and, in the context of MS, help temper the inflammation triggered by attacks on the myelin sheath.

T cells use signals from different proteins to respond to threats in the body, helping fight off bacteria, heal up wounds or tackle cancer. Tregs play an important counter-balancing role in this process, preventing out-of-control T cell responses that typify an autoimmune response, like that seen in MS. The UCI scientists zeroed in on one of these protein triggers for T cell responses called Piezo1, which research has shown to be important in regulating a range of bodily functions.

These include red blood cell volume, blood pressure and bone development. Piezo1 is also known to guide certain T cell function, though how it influences immune responses specifically had not yet been thoroughly explored. To do so, the scientists drew up experiments using mouse models of MS in which the Piezo1 protein was genetically deleted, with the rodents showing lower disease severity as a result.

“We found that Piezo1 selectively restrains Treg cells, limiting their potential to mitigate autoimmune neuroinflammation,” says study author Michael D. Cahalan. “Genetically deleting Piezo1 in transgenic mice, resulted in an expanded pool of Treg cells, which were more capable of effectively reducing neuroinflammation and with it the severity of the disease.”

These experiments revealed some other useful new insights about the function of Piezo1 that the scientists did not expect. While the protein is known drive some T cell functions, the researchers unearthed a variety of functions that it seemingly has no part in, including interactions with the lymph nodes, as well as the cells' proliferation and differentiation into other T cell types. This selectivity makes Piezo1 a promising target for MS therapies.

“We found the role of Piezo1 appears to be quite specific to Tregs," says study author Shivashankar Othy. "Therefore, targeting Piezo1 might be a new and ideal strategy to cure MS while preserving the immune system’s ability to fight new infections."

The research was published in the journal Science Advances.

Source: University of California, Irvine