News Blocking Kidney Protein Prevents Progression in MS Mouse Model Blocking Kidney Protein Prevents Progression in MS Mouse Model by Lindsey Shapiro, PhD | June 8, 2022 Share this article: Share article via email Copy article link 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 theĀ American Journal of Physiology – Cell Physiology. Recommended Reading May 25, 2022 News by Marta Figueiredo, PhD ‘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 autoimmuneĀ disease. To determine whether such inhibition might ease MS symptoms,Ā 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 ā and in a downstream protein called glutathione peroxidase 1 (GPx1) ā 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]āROS axis may be a potential therapeutic target for treating autoimmune diseases,” the researchers concluded. Print This Page About the Author Lindsey Shapiro, PhD Lindsey earned her PhD in neuroscience from Emory University in Atlanta, where she studied novel therapeutic strategies for treatment-resistant forms of epilepsy. She was awarded a fellowship from the American Epilepsy Society in 2019 for this research. Lindsey also previously worked as a postdoctoral researcher, studying the role of inflammation in epilepsy and Alzheimerās disease. Tags reactive oxygen species, Th17 cells, Tregs
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