ERC funds research link between body clock and immune system
Researchers at Trinity College Dublin, Ireland, and the University of Pennsylvania, United States, have uncovered an important link between the human body clock and the immune system that will have relevance to the treatment of inflammatory and infectious diseases.
Their study, part-funded by the European Research Council (ERC), shows how the biological clocks inside important white blood cells (called macrophages) stop when they are exposed to bacteria; crucially, stopping the clock allows the cells to become active and inflamed. The complex mechanism involves a factor called miR155, which destroys a key cog in the clock’s mechanism called BMAL1. This allows the macrophage to make a number of inflammatory proteins that effectively wake up and activate the immune system.
Scientists have known for a long time that the immune system and body clock are interconnected and that our immune system responds differently to bacteria depending on the time of day at which it is exposed. The researchers found that this was dependent on the level of clock protein (BMAL1) present in the macrophage. BMAL1 functions as a ‘dampener’ of the immune system and, because levels are lower at night, the immune system can be more active.
A less active immune system during the day (when BMAL1 levels are higher) may mean that our bodies do not over-react to infections, which are more likely to occur when we are active and meeting sources of infection. However, if our systems need to mount a big response, such as an infection with a virus or bacteria, then macrophages can reduce BMAL1 levels; this is carried out via miR-155.
Commenting, Professor Garret FitzGerald, joint senior author from the University of Pennsylvania, said: “There may be times, such as during an acute infection, where it’s advantageous for the immune system to use miR-155 to stop the macrophage clock and allow the body to clear the infection. When inflammation is present for long periods of time, as is the case for patients with a chronic disease like rheumatoid arthritis, this constant targeting of the clock may actually worsen disease.”
The results are published in the journal Proceedings of the National Academy of Sciences USA.
