Your day is run on a 24-hour cycle, most likely involving too little sleep, a lot of coffee, and the nine to five work grind. While you get past your 2 PM slump your cells follow their 24-hour molecular clock that dictates their behavior, termed circadian rhythm. Circadian rhythms are found in most living things and dictate physical, mental, and behavioral changes that follow a daily cycle. A recent study published in the Proceedings of the National Academy of Sciences (PNAS), examined the role the body clock plays in regulating the immune response.
Growing evidence shows that the innate immune system possesses a molecular clock that impacts functions such as phagocytosis, cytokine production, and inflammation as well as antibacterial and antiviral activity based on the time of day. Researchers hypothesize that these changes in the immune response based on the clock help prepare an organism for pathogenic threats allowing for optimization of clearance and recovery. The circadian rhythms of the molecular clock are maintained by transcriptional and translational feedback loops and orchestrated by the bodies ‘master clock’. The master clock resides in the suprachiasmatic nucleus of the hypothalamus and keeps synchrony between peripheral clocks and the external environment, providing rhythm across a range of biological processes such as metabolism and immune function. While this anticipatory mechanism is known to help organisms respond to daily changes in the external environment, the mechanisms underlying molecular basis has yet to be elucidated.
The recent study conducted by researchers of the Royal College of Surgeons of Ireland and the Trinity College Dublin set out to unravel the molecular mechanism behind this body clock control. A core protein involved in this molecular clock, BMAL1, forms a heterodimeric partnership with the protein CLOCK to induce rhythmic expression in various clock-controlled genes. Reactive oxygen species (ROS) serve as signaling molecules for the immune response, BMAL1 plays a role in regulating this response in multiple tissues. Previous studies show that deletion of the genes encoding for BMAL1 leads to increased oxidative stress due to the build-up of ROS leading to increased levels of cytokine IL-1ß which is responsible for producing symptoms of fever and inflammation. The study, conducted by senior author Dr. Annie Curtis of the Royal College of Surgeons of Ireland, observed that BMAL1 regulates the level of antioxidant response proteins to control the level of the essential inflammatory molecule IL-1ß from macrophages.
The study shines a light on why individuals who experience disruptions in the body click are more susceptible to inflammatory conditions such as asthma. A better understanding of how the body clock controls inflammation could lead to new therapeutic options and determination of the best time of day for treatment. "The findings although at a preliminary stage, offers new insights into the behavior of inflammatory conditions such as arthritis and cardiovascular disease which are known to be altered by the body clock," said the studies first author Dr. Jamie Early.
To learn more about your circadian rhythm watch the video below!
Sources: Proceedings of the National Academies of Sciences, National Institute of General Medical Sciences, Journal of Cell Biology
