Autoimmune diseases affect nearly 4% of the world’s population, the most common being Crohn’s disease, psoriasis, multiple sclerosis, and rheumatoid arthritis. New research has identified natural compounds that may offer new ways to treat these debilitating diseases.
T cells are key to the body’s immune response to attack pathogens and infections. In autoimmune diseases, the immune response is defective and T cells begin attacking healthy cells and tissues, but the underlying mechanisms are poorly understood.
Our adaptive immune system responds to the specific pathogen it encounters and creates a long-lasting “memory” so the body knows how to fight it if it encounters that pathogen again. Th) cells are a type of T cell that play a central role in releasing cytokines that activate other immune cells to fight invading pathogens.
Interleukin-17 (IL-17), one of the cytokines important in the body’s inflammatory response, is secreted by a subtype of Th cells called Th17 cells. Th17 cells enhance the immune response and accumulate immune cells at sites of inflammation. However, when overactivated, it attacks healthy cells and causes autoimmunity.
A new study from Japan focuses on the role that Th17 cells play in autoimmune diseases. Researchers began by looking at glycolysis, the metabolic process by which glucose is converted into energy for fuel cells. It is also involved in the creation of Th17 cells.
“Interestingly, excessive glycolysis appears to suppress the activity of Th17 cells,” said Tsung-Yen Huang, lead author of the study. “Therefore, we hypothesized that molecules produced during glycolysis might inhibit cells.”
Glycolysis produces a byproduct called phosphoenolpyruvate (PEP). The researchers found that introducing additional Her PEP into cells prevented Th17 cell maturation and suppressed IL-17 production, thereby reducing the body’s inflammatory response. Importantly, addition of PEP to cells had no significant effect on the glycolytic process or activation of her T cells.
Digging deeper into the processes underpinning PEP’s inhibitory action, they found that a protein called JunB promotes Th17 maturation by binding to a specific set of genes. Further experiments showed that PEP treatment blocked JunB activity and inhibited the generation of Th17 cells.
The researchers tested their findings in mice with autoimmune brain disease and found that daily administration of PEP halted the production of Th17 cells and reduced Th17-dependent autoimmune responses. .
“The key to the development of autoimmune diseases, and how to suppress this development, lies in our cells, but the underlying mechanisms have always been unknown.” We have shed light on compounds that can suppress .”
This study may present a new way to treat autoimmune diseases without interfering with the key metabolic process of glycolysis. Researchers want to improve the process before proceeding to human clinical trials.
“Our results demonstrate the clinical potential of PEP. But first, we need to increase its efficiency.”
The study was published in a journal cell report.
Source: Okinawa Institute of Science and Technology Graduate University
