An international group of scientists from the U.S., Canada, Germany, and Russia has shown that itaconate can suppress the proinflammatory activity of macrophages.
The work, which united scientists from Washington University in St. Louis, ITMO University, McGill University, and the Max Planck Institute of Immunobiology and Epigenetics, was based on the study of macrophages, which play a critical role in fighting pathogens.
An important feature of macrophages is their ability to switch between different states depending on the concentration of various substances in the body.
An in-depth study of macrophage metabolism during their transition from the inactive to proinflammatory state helped researchers identify the substance that could suppress macrophage-related inflammations.
Itaconate is produced by macrophages when they switch from the M0 inactive state to the M1 proinflammatory state. “Itaconate sets the bar controlling M1 macrophage formation,” says Alexey Sergushichev, one of the authors of the paper and Ph.D. student at ITMO University.
“Without this substance, the inflammation would increase more than required. In the future, with the help of itaconate, it will be possible to artificially manipulate the transition of macrophages from M0 to M1, meaning the possibility of restraining inflammations. The influence of itaconate on macrophages is a delicate mechanism that can ensure high selectivity of the immune system regulation.”