Excessive sugar consumption causes the immune system to attack your own body
People who consume excessive amounts of sugar and other carbohydrates over a long period of time have an increased risk of developing autoimmune diseases. The immune system of such patients attacks the body's own cells, causing, for example, chronic inflammatory bowel disease, thyroid disease and type 1 diabetes. The study by German scientists will help identify new targets for therapy for a number of such diseases.
The molecular mechanisms underlying autoimmune diseases are multi-layered and complex. In their study, scientists from the Julius and Maximilian University of Würzburg in Germany have managed to decipher new details of these processes. Their work, published in the journal Cell Metabolism, supports the common notion that excessive consumption of glucose and other carbohydrates directly promotes pathogenic functions in immune system cells and, conversely, that a low-calorie diet may help treat immune diseases.
Together with his team, Dr. Martin Väth from the Institute of Systems Immunology at the University of Würzburg has shown the specific role of a specific glucose transporter protein, GLUT3, found in the membrane of many cells, particularly immune cells. The scientists found that in immune T-cells, this protein performs, in addition to the main function - the transfer of glucose into the cell for energy production - and additional regulatory functions.
T cells, or T lymphocytes, play an important role in the acquired immune response by recognizing and destroying cells carrying foreign antigens. Scientists have focused on a particular group of T cells, the recently discovered type 17 T-helper cells, also called Th17-lymphocytes, which play an important role in the regulation of inflammatory and autoinflammatory processes. The primary function of T-helper cells is to recognize threats and enhance the immune response by activating other immune cells in the body.
“Th17 cells normally express large amounts of GLUT3 protein by incorporating it into their membrane,” explains Dr. Vath. After being taken up by the GLUT3 protein, glucose, after undergoing a series of reactions in the mitochondria and cytoplasm of the cells, is finally converted into an important compound for any cell - acetyl-coenzyme A (acetyl-CoA). Acetyl-CoA, in turn, is involved in many metabolic processes (including energy production), and in immune inflammatory cells, Th17 also performs additional regulatory functions.
Dr. Vet and his team have shown that this metabolic intermediate can also regulate the expression activity of various DNA sites. Specifically, acetyl-CoA causes Th17 lymphocytes to produce more pro-inflammatory cytokines, signaling molecules that tell other immune cells to initiate or amplify the inflammatory process. Thus, excessive glucose consumption leads to increased accumulation of acetyl-CoA in Th17-lymphocytes, which directly affects the activity of pro-inflammatory genes.
According to the researchers, the findings open the way to the development of new approaches of targeted therapy for autoimmune diseases. For example, blocking GLUT3-dependent synthesis of acetyl-CoA by a dietary supplement, hydroxycitrate, used to treat obesity. This may mitigate pathogenic functions of Th17 cells and attenuate inflammatory-pathologic processes by suppressing excessive immune and autoimmune responses.
The so-called metabolic reprogramming of T cells opens new possibilities for the treatment of various autoimmune diseases, such as chronic inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and thyroid diseases, as well as type 1 diabetes (in which insulin-producing cells are destroyed) without reducing the protective functions of immune cells.