Blocking Kidney Protein Prevents Progression in MS Mouse Model

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

Share this article:

Share article via email
MS research myelin repair | Multiple Sclerosis News Today | tenacin proteins | illustration of a mouse in a lab

A protein called nephronectin mediates autoimmunity in a mouse model of multiple sclerosis (MS), and blocking this protein was found to prevent disease progression and processes that drive T-cells toward an inflammatory state, researchers reported.

Study findings support nephronectin, a protein involved in kidney development, as a promising treatment target for MS and other autoimmune diseases, its investigators said.

The study, “Nephronectin influences EAE development by regulating the Th17/Treg balance via reactive oxygen species,” was published in the American Journal of Physiology – Cell Physiology.

Recommended Reading
multiple sclerosis disability progression | Multiple Sclerosis News Today | illustration of person undergoing MRI

‘Silent Progression’ in Relapsing MS Linked to Significant Brain Atrophy

Most MS treatments are designed to target the mistaken autoimmune attacks that drive the disease, but many are accompanied by significant side effects, including an increased risk of serious infections.

Nephronectin has emerged as a potential target for managing autoimmunity in MS. The protein has been shown to be at unusually higher levels in the blood of mice with experimental autoimmune encephalitis (EAE), a common mouse model of MS. Inhibiting, or blocking, the protein also eased symptoms in a mouse model of inflammatory arthritis, another autoimmune disease.

To determine whether such inhibition might ease MS symptoms, researchers at Fukuyama University, in Japan, in collaboration with Immuno-Biological Laboratories, used an anti-nephronectin antibody to block the protein in EAE mice. They found that the antibody significantly inhibited disease progression in the model.

Additional work uncovered the mechanisms through which nephronectin contributes to inflammation. Researchers found that it binds to and increases the levels of another protein called selenoprotein P, which is known to stimulate the growth and activity of T-cells, an immune cell implicated in MS progression.

Molecularly, this rise in selenoprotein P levels — and in a downstream protein called glutathione peroxidase 1 (GPx1) — lowered the levels of reactive oxygen species (ROS), a group of molecules that help determine the fate of differentiating T-cells. In the presence of high ROS levels, T-cells acquire a more immunosuppressive role that dampens inflammatory responses. But when ROS levels are low, T-cells take on a pro-inflammatory function that contributes to autoimmunity.

Treating EAE mice with the anti-nephronectin antibody prevented these changes. In the absence of nephronectin, selenoprotein P and GPx1 levels were lower and ROS levels were normalized, which promoted T-cell differentiation into immunosuppressive regulatory T-cells rather than pro-inflammatory T-cells (mainly T-helper 17, or Th17, cells).

Importantly, these molecular changes associated with antibody treatment were also associated with lesser inflammation and a lower degree of demyelination in the spinal cords of EAE mice. Demyelination is the loss of myelin, the protective substance surrounding nerve cells, which is the target of MS autoimmune attacks.

These findings “suggest that the [nephronectin]ROS axis may be a potential therapeutic target for treating autoimmune diseases,” the researchers concluded.

Questions to Ask Your Doctor If You’re Newly Diagnosed

Illustration of doctor an patient talked
We consulted some of our community contributors at MS News Today and came up with 12 questions people should consider asking their doctors after an MS diagnosis.

Check it out by clicking here.

Dancing Doodle

Did you know some of the news and columns on Multiple Sclerosis News Today are recorded and available for listening on SoundCloud? These audio news stories give our readers an alternative option for accessing information important for them.

Listen Here