Examination of a complete data set on cells essential to the mammalian immune system shows that our ability to fight off may be more dependent on daily circadian cycles than we previously anticipated.
Imbalances in circadian rhythms, the process that keeps our bodies in harmony with the day / night cycles, are increasingly linked to diabetes, cancer, Alzheimer’s, and many other diseases. A study published today in Genome Research shows the activity of macrophages -; cells within us that seek out and destroy invaders like bacteria -; time can cause daily changes in their responses to pathogens and stress through circadian control of metabolism.
In this study, Jennifer Hurley, Richard Baruch MD Professor of Career Development in Biological Sciences at Rensselaer Polytechnic Institute and senior author of this study, and her team examined the levels of RNA and protein levels the macrophages change over two days. “We’ve shown that macrophage behavior has an incredible amount of circadian time, but the clock gives macrophages time in unexpected ways,” Hurley said.
The circadian system is made up of a set of basic clock proteins that encapsulate the day / night cycle by causing daily oscillations in levels of enzymes and hormones, and ultimately affecting known parameters. such as body temperature and the immune response. This molecular clock marks time through an autonomous cycle of protein production and decomposition. Clock “positive” element proteins override “negative” element proteins, which themselves inhibit the production of positive element proteins until the proteins of the negative element proteins decompose, thus creating a knowledge circle -a negative feedback that occurs once every 24 hours.
Advanced element proteins also regulate variants in a large number of gene expression, called messenger RNA or mRNA. Genetic guidance is transcribed from DNA to mRNA, which is then used as a recipe for accumulating proteins, building blocks of cell function. It has long been accepted that the levels of each subsequent step could be predicted from the previous one. If so, oscillating mRNA would correspond to oscillating levels of cellular proteins, so if one could monitor mRNA, they would know which proteins the circadian clock was making. control in the cell.
However, this study showed that this paradigm may not always be true. Analysis of the macrophage data revealed a significant imbalance between the proteins and mRNAs controlled by the circadian clock. These data were parallel to research published in Cellular systems in 2018 by Hurley laboratory, showing that about 40% of oscillating proteins are in the fungal and circadian model system, Neurospora crassa, they did not have a corresponding oscillating mRNA.
But the scale of the difference in macrophages surprised us. Eighty percent of the oscillating mRNA-opening proteins are not involved in macrophages. That means we were missing out on a lot of time as the clock timed the defense. “
Jennifer Hurley, Richard Baruch MD Professor of Career Development in Biological Sciences at Rensselaer Polytechnic Institute
Hurley’s team, in collaboration with Annie Curtis ’lab at the Royal College of Surgeons in Ireland (RCSI), was able to predict and then show that the clock regulates metabolism to give time to a major immune functions in macrophages. To do this, researchers from RCSI looked at the energy-generating mitochondria of macrophages, showing the rhythm by which the organs separate to generate energy and reunite at the resting stage. The Hurley laboratory was then able to show that the timing of major immune processes was controlled by the changes in energy production resulting from the cleavage and melting of mitochondria.
“Our data indicate that rhythms need to be monitored at an entirely new level,” said Curtis, a senior lecturer at RCSI. “It also means that our bodies are timed by our circadian clocks. more than we thought. ”This circadian moment of the immune system has an impact on human health, disease treatment, and vaccine effectiveness.
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Rensselaer Polytechnic Institute