OKINAWA: Japanese researchers have identified a chemical used to treat a variety of autoimmune conditions, including rheumatoid arthritis and multiple sclerosis. Some diseases develop when the body’s immune system is damaged. Instead of attacking germs and disease, the immune system attacks healthy cells and tissues.
The consequences of autoimmune disorders can be devastating for the millions of people who experience them worldwide. Rheumatoid arthritis causes severe joint pain, and multiple sclerosis can impair brain and spinal cord function.
“The key to the development of autoimmune diseases and thus the way to inhibit this development lies in our cells, but the underlying mechanism has always been unclear,” said Prof. Hiroki Ishikawawho is in charge Immune signaling unit according to Okinawa Institute of Science and Technology (OIST). “Now, our recent research has uncovered a compound that suppresses the development of these diseases.”
Professor Ishikawa explained that the research, published in the journal Cell Reports, could lead to the development of treatments for autoimmune diseases.
The study focused on T helper 17 cells or Th17 cells. Th17 cells are a type of T-cell – a group of cells that make up the main parts of the immune system. Abundant in our gut, these cells evolved to help fight invading pathogens, but sometimes they become overactivated and mistake normal, healthy tissue for pathogens, resulting in 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 the cells. Glycolysis is essential for the growth of not only Th17 cells but also various cells in our body.
“What’s interesting about this excessive glycolysis is that it seems to suppress the activity of Th17 cells,” said first author Mr. Tsung-Yen. Juan, PhD candidate in the Immune Signaling Unit. “So we hypothesized that molecules produced during glycolysis could inhibit cells.”
Administer phosphoenolpyruvate, or PEP briefly. This chemical compound is a metabolite formed when glucose is converted into energy. Because it is part of an important process, our body produces PEP every day. The researchers found that treatment with PEP was able to inhibit the maturation of TH17 cells, leading to a reversal of the inflammatory response.
Mr. Huang explained that this was a confusing result at first because it contradicted all other research on the topic, but he decided to persevere and take a closer look at what was going on.
The research led them to a protein called JunB, which is essential for the maturation of Th17 cells. JunB promotes Th17 maturation by binding to a specific set of genes. The researchers found that PEP treatment inhibited the generation of Th17 cells by blocking JunB activity.
Armed with this knowledge, the researchers set out to treat mice with autoimmunity-induced neuroinflammation with PEP. This disease is very similar to multiple sclerosis and these mice showed positive signs of recovery. Scientists have now filed a patent to continue this research.
“Our results demonstrate the clinical potential of PEP,” explained Mr. Huang. “But first we need to improve its effectiveness.”
The consequences of autoimmune disorders can be devastating for the millions of people who experience them worldwide. Rheumatoid arthritis causes severe joint pain, and multiple sclerosis can impair brain and spinal cord function.
“The key to the development of autoimmune diseases and thus the way to inhibit this development lies in our cells, but the underlying mechanism has always been unclear,” said Prof. Hiroki Ishikawawho is in charge Immune signaling unit according to Okinawa Institute of Science and Technology (OIST). “Now, our recent research has uncovered a compound that suppresses the development of these diseases.”
Professor Ishikawa explained that the research, published in the journal Cell Reports, could lead to the development of treatments for autoimmune diseases.
The study focused on T helper 17 cells or Th17 cells. Th17 cells are a type of T-cell – a group of cells that make up the main parts of the immune system. Abundant in our gut, these cells evolved to help fight invading pathogens, but sometimes they become overactivated and mistake normal, healthy tissue for pathogens, resulting in 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 the cells. Glycolysis is essential for the growth of not only Th17 cells but also various cells in our body.
“What’s interesting about this excessive glycolysis is that it seems to suppress the activity of Th17 cells,” said first author Mr. Tsung-Yen. Juan, PhD candidate in the Immune Signaling Unit. “So we hypothesized that molecules produced during glycolysis could inhibit cells.”
Administer phosphoenolpyruvate, or PEP briefly. This chemical compound is a metabolite formed when glucose is converted into energy. Because it is part of an important process, our body produces PEP every day. The researchers found that treatment with PEP was able to inhibit the maturation of TH17 cells, leading to a reversal of the inflammatory response.
Mr. Huang explained that this was a confusing result at first because it contradicted all other research on the topic, but he decided to persevere and take a closer look at what was going on.
The research led them to a protein called JunB, which is essential for the maturation of Th17 cells. JunB promotes Th17 maturation by binding to a specific set of genes. The researchers found that PEP treatment inhibited the generation of Th17 cells by blocking JunB activity.
Armed with this knowledge, the researchers set out to treat mice with autoimmunity-induced neuroinflammation with PEP. This disease is very similar to multiple sclerosis and these mice showed positive signs of recovery. Scientists have now filed a patent to continue this research.
“Our results demonstrate the clinical potential of PEP,” explained Mr. Huang. “But first we need to improve its effectiveness.”
