Scientists interested in manipulating the immune system, either to suppress autoimmune reactions or to boost anti-cancer and anti-pathogenic responses, hit a gold mine in a recent study. They found that dendritic cells of the immune system have a “secret stash” of energy that serves as the initial and primary source of power during the immune response.
Dendritic cells are antigen-presenting cells; this means that they detect foreign cells in the body and present them to effector T cells. Should T cells deem it necessary, they mount an attack. An attack is beneficial if there is indeed a pathogenic invasion on the way, but if the T cells accidentally begin an unwarranted attack, autoimmune disease can occur. The ability to control the activity of dendritic cells would grant scientists a large amount of power over regulating the immune response.
The energy stash University of Vermont scientists discovered was an internal store of glycogen, a glucose polymer used as carbohydrate storage for all animals, not just humans. In the past, scientists have focused their studies on dendritic cells’ external energy storage. However, they found that the internal glycogen supply is in fact the first place dendritic cells extract energy when they need it.
Co-author of the Cell Metabolism study Phyu Thwe says that timing is extremely important for understanding the immune response, so knowing the order in which dendritic cells use energy is vital. “In any kind of immune protection scenario it is absolutely a race against time between the microbe and mammalian immune response,” Thwe explained.
"By either enhancing or depleting this sugar warehouse within the cell, the hope would be that we could either influence or dampen immune reactions," explained another study author, Eyal Amiel. "What we're really in the business of is finding new switches to toggle to that effect, and this finding provides us with a new regulatory target that regulates immune activity."
Amiel, Thwe, and other researchers looked at dendritic cell activity when their access to internal glycogen was inhibited. As expected, the cells were less effective at communicating with T cells, and the immune response was subsequently suppressed. Additionally, Amiel says that this effect is probably not specific to dendritic cells; they could use the same approach to control the activity of other immune cells too.
In the future, the team from the University of Vermont will continue their studies on altering dendritic cells’ internal glycogen stores to control their ability. But first, they must assess how the cells are impacted in the long run. Even people with autoimmune diseases need the immune system to be somewhat active to have protection from bacteria and viruses. Scientists want to manipulate dendritic cells temporarily, not permanently.
Sources: Oregon State University, The Rockefeller University, University of Vermont