Japanese scientists have revealed a chemical compound that could be used for the treatment of various autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. These diseases occur when the body’s immune response becomes nervous. The immune system, which normally attacks pathogens and infections, instead attacks healthy cells and tissues. For the millions of people who suffer from autoimmune diseases around the world, the result can be debilitating: rheumatoid arthritis causes excessive joint pain, while multiple sclerosis can disable brain and spinal cord function.
The key to the development of autoimmune diseases, and therefore how to inhibit this development, lies in our cells, but the underlying mechanism has still not been clear. Now, our recent research has brought to light a compound that may suppress the development of these diseases. »
Teacher. Hiroki Ishikawa, Chief, Immune Signal Unit, Okinawa Institute of Science and Technology (OIST)
Professor Ishikawa went on to explain that this research, published in Cell reportscould lead to the development of treatments for autoimmune diseases.
Research has focused on helper T cells 17, or Th17 cells. Th17 cells are a type of T cell, a group of cells that make up most of the immune system. These cells, which exist in large numbers in our intestines, have evolved to help us fight off invading pathogens, but sometimes they get overactivated and mistake normal, healthy tissue for pathogens, leading to autoimmunity. The generation of Th17 cells requires glycolysis, a metabolic process in which glucose is broken down and converted into energy to meet the metabolic needs of cells. Glycolysis is essential for the growth of not only Th17 cells, but also various cells in our body.
“Interestingly, excessive glycolysis appears to suppress Th17 cell activity,” said first author Dr. Tsung-Yen Huang, PhD candidate in the Immune Signaling Unit. “We therefore hypothesized that the molecules produced during glycolysis could inhibit the cells. »
Enter phosphoenolpyruvate, or PEP for short. This chemical compound is a metabolite produced when glucose is converted into energy. Since it is part of such an important process, PEP is generated every day in our body. The researchers found that PEP treatment can inhibit TH17 cell maturation, leading to resolution of the inflammatory response.
Dr. Huang explained that this was, at first, a confusing result, as it ran counter to all other research on the subject, but he decided to persevere and take a closer look. what might happen.
The search led them to a protein called JunB, which is essential for Th17 cell maturation. JunB promotes Th17 maturation by binding to a set of specific genes. The researchers found that PEP treatment inhibits the generation of Th17 cells by blocking the activity of JunB.
Armed with this knowledge, the researchers then treated mice with neuroinflammation caused by autoimmunity with PEP. This disease is very similar to multiple sclerosis and these mice showed positive signs of recovery. The scientists have now filed a patent to continue this research.
“Our results show the clinical potential of PEP,” Huang explained. “But first we need to increase its efficiency. »
In the past, researchers interested in developing a treatment for autoimmune diseases often sought to inhibit glycolysis and therefore Th17 cells. But glycolysis is essential for various cell types in the body, and inhibiting it could have significant side effects. PEP has the potential to be used as a treatment without causing such side effects.