Immune response may rely on circadian rhythms, study finds

Data analysis on cells essential to the mammalian immune system found that the ability to fight disease may rely more heavily on daily circadian cycles than previously assumed, according to new research published in the journal Genome Research.

For the study, researchers from the Rensselaer Polytechnic Institute investigated how the levels of RNA and proteins in macrophages, cells within us that seek and destroy intruders like bacteria, change over two days. 

Malfunctions in circadian rhythms, the process that keeps our bodies in tune with the day and night cycles, are increasingly associated with diabetes, cancer, Alzheimer's, and many other diseases, the researchers said. The research shows that the activity of macrophages may time daily changes in their responses to pathogens and stress through the circadian control of metabolism.

The circadian system is comprised of a set of core clock proteins that anticipate the day and night cycle by causing daily oscillations in levels of enzymes and hormones, and ultimately affecting physiological parameters such as body temperature and the immune response. This molecular clock marks time through a self-regulating cycle of protein production and decay. The "positive" element proteins of the clock trigger production of the "negative" element proteins, which in turn block production of positive element proteins until the negative element proteins decay, thus creating a negative feedback cycle that occurs once every 24 hours, according to the study.

Positive element proteins also regulate fluctuations in a substantial number of gene products, known as messenger RNA or mRNA, the researchers said. Genetic instructions are transcribed from DNA to mRNA, which are then used as a recipe for assembling proteins, the functional building blocks of the cell. It has long been assumed that the levels of each subsequent step could be predicted from the previous. If that were the case, oscillating mRNA would correspond with oscillating levels of cellular proteins, and therefore, if one could track mRNA, they would know what proteins the circadian clock controlled in the cell.

"We have shown there is an incredible amount of circadian timing of macrophage behavior,” said Jennifer Hurley, MD, senior author of the study and assistant professor of biological sciences, in a statement, “but the clock is timing macrophages in unexpected ways.”