Aerobic glycolysis (aerobic glycolysis) is a metabolic pathway that is essential for the survival and proliferation of effector T cells in the body. It can regulate the differentiation of T helper 17 cells (Th17 cells), but the molecular mechanism behind this regulation is not clear to the researchers.recently, Published in a study entitled "Phosphoenolpyruvate regulates the Th17 transcriptional program and inhibits autoimmunity" in the international journal Cell Reports, Scientists from institutions such as the Okinawa University of Science and Technology have found that, A special compound that could be used to help treat multiple autoimmune diseases in humans, Such as multiple sclerosis and rheumatoid arthritis; When the body's immune response problems, the disease will occur. Usually help attack pathogens and infection of the immune system will attack the body's healthy cells and tissues, for global autoimmune disease of millions of people, the result may be very serious, rheumatoid arthritis can lead to excessive joint pain, and multiple sclerosis can promote the function of the brain and spinal cord loss.
Researcher Professor Hiroki Ishikawa said that the key to the development of autoimmune diseases lies in the body's own cells, but the molecular mechanism behind it is not immediately clear. Now we have found a particular compound that may inhibit the disease, and it may also help develop new therapies for autoimmune diseases in humans.
Article, the researchers focus on T auxiliary 17 cells (Th17 cells), it is a kind of special T cells (constitute the main part of the body immune system), these cells usually exist in the body gut, and it will evolve to help resist the invasion of the body pathogen, but sometimes its excessive activation and wrong normal healthy tissue as a pathogen, leading to the occurrence of autoimmune diseases. The production of Th 17 cells requires glycolysis (a metabolic process in which glucose is decomposed and converted into energy to support the metabolic needs of the cell), and glycolysis is important not only important for the growth of Th 17 cells, but also for various types of cells in the body.
Interestingly, the researchers say, excessive glycolysis seems to inhibit the activity of Th 17 cells, so we hypothesized that the specific molecules produced during glycolysis would inhibit the cellular function of the cells. Is called phosphoenolpyruvate (PEP, phosphoenolpyruvate) compound is glucose is converted into energy after a metabolite, because it is such an important part of the process, so the body produces PEP every day, the researchers found that the use of PEP therapy can inhibit Th 17 cells mature, which will lead to the body inflammatory response.
This was initially a confusing result because it contradict all other studies on the subject, but we decided to go deeper into why this happened, researcher Huang explained. Then the researchers discovered a special protein called JunB, which is important for the maturation of Th 17 cells. JunB promotes a maturation of Th 17 cells by combining a specific class of genes. The researchers found that PEP therapy inhibits Th 17 cells by blocking the activity of JunB. Based on the results, the researchers began using PEP therapy to treat mice with autoimmune neuroinflammation, a disease very similar to multiple sclerosis, and then showed positive signs of recovery, who have applied for a patent and will continue to study it later.
The present study highlights the clinical potential of PEP, but first the investigators need to increase its efficiency. In the past, researchers were interested in developing new therapies for human autoimmune diseases, often focusing at how to inhibit glycolysis to inhibit Th 17 cells, but the glycolysis process is important for many types of cells in the body to cause serious side effects; PEP may be potentially used as a therapy without such side effects.
Taken together, the relevant results suggest that PEP can link aerobic glycolysis to the transcriptional program of Th 17, which perhaps reveals the potential therapeutic potential of PEP in autoimmune diseases.
