Genome Res: The circadian rhythm clock may control the function of macrophages

January 19, 2021 // -- A detailed database of essential cells of the mammalian immune system suggests that humans may be more resistant to disease than previously thought, relying more on the body's daily circadian clock;
In a recent study published in the international journal Genem Research, scientists from the Renssler Institute of Technology and others found that macrophages that can find and destroy invasive pathogens, such as bacteria, can change responses to external pathogens and stresses by controlling the circadian rhythms of the body's metabolism.
In this study, researchers analyzed how RNA and protein levels in macrophages changed over a two-day period, and now we've shown that macrophage behavior has an incredible circadian rhythm, but the clock is timing macrophages in an unexpected way. The
circadian rhythm system consists of a core set of clock proteins that predict circadian cycles by causing fluctuations in the body's daily enzyme and hormone levels, and ultimately affect the body's physiological parameters, such as the body's body temperature and immune response, which can mark time through a self-regulating mechanism of protein production and decay.
the active elemental protein in the clock triggers the production of the elemental protein, which in turn blocks the production of the positive element protein until the negative element protein decays, resulting in a negative feedback loop that occurs every 24 hours.
photo source: Rensselaer Polytechnic Institute forward element proteins regulate fluctuations in mRNA, a large number of gene products, and gene instructions can be transprinated from DNA to mRNAs and then used as a formula for assembling proteins.
Scientists have long assumed that the level of each subsequent step can be predicted from the previous steps, and if so, fluctuating mRNAs will correspond to the fluctuating levels of proteins in cells, so if mRNAs can be tracked, researchers will know which proteins in the cells can be controlled by the biological clock.
This study suggests that this pattern may not always be correct, and an analysis of the macrophage database suggests that there may be a large number of mismatches between proteins affected by circadian rhythm clocks and mRNAs, consistent with previous studies, which show that about 40 percent of the fluctuating proteins in the fungal and biological clock models, Neurospora crassa, do not have a corresponding fluctuating mRNA.
researcher Hurley said: 'We were surprised by the size of the difference between macrophages, with 80 per cent of the proteins that fluctuate being associated with mRNAs that fluctuate in macrophages, which means we may not really know how the clock is timed.'
researchers are now able to predict and prove that the biological clock regulates metabolism as a key immune function timing for macrophages.
The researchers tracked the mitochondrials that produce energy in macrophages, which may reveal the rhythms of cell division that produce energy and re-binding in a resting state; the timing of critical immune processes may be controlled by changes in energy production, which are derived from mitochondrial division and fusion processes.
The researchers concluded that the data in this paper suggest that we need to track the circadian rhythms of the body at a whole new level, which means that our bodies are more dependent on the biological clock than we thought, and that the circadian rhythms of the immune system have a significant impact on the body's health, disease therapy and vaccine effectiveness.
() Original source: Emily J Collins, Mariana P Cervantes-Silva, George A Timmons, et al. Post-transcriptional circadian regulation in macrophages organizes temporally distinct immunometabolic states, Genome Res. 2021 Jan 12. doi: 10.1101/gr.263814.120