Summary: Researchers shed light on how the circadian rhythm and time of day impact immune response in autoimmune diseases. The findings could help in the development of new treatments to tackle a range of autoimmune disorders.
Source: TCD.
Insights into how the body clock and time of day influence immune responses are revealed today in a study published in leading international journal Nature Communications. Understanding the effect of the interplay between 24-hour day-night cycles and the immune system may help inform drug-targeting strategies to alleviate autoimmune disease.
Circadian rhythms or 24-hour rhythms are generated by the body clock, allowing us to anticipate and respond to the 24-hour cycle of our planet. Maintaining a good body clock is generally believed to lead to good health for humans, and disrupting the circadian rhythm (for example, working night shifts) has been associated with immune diseases such as multiple sclerosis; however, the underlying molecular links have been unclear.
In the new study, Professor Kingston Mills and Dr Caroline Sutton of Trinity College Dublin, and Dr Annie Curtis of RCSI (Royal College of Surgeons Ireland), and colleagues show that immune responses and regulation of autoimmunity are affected by the time of the day when the immune response is activated.
Using mice as a model organism, they show that a master circadian gene, BMAL1, is responsible for sensing and acting on time-of-the-day cues to suppress inflammation. Loss of BMAL1, or induction of autoimmunity at midday instead of midnight, causes more severe experimental autoimmune encephalomyelitis, which is essentially an analogue of multiple sclerosis in mice.
Professor of Experimental Immunology at Trinity, Kingston Mills, said: “In the year that the Nobel Prize in Medicine was awarded for discoveries on the molecular mechanisms controlling the circadian rhythm, our exciting findings suggest that our immune system is programmed to respond better to infection and insults encountered at different times in the 24-hour clock. This has significant implications for the treatment of immune-mediated diseases and suggests there may be important differences in time of day response to drugs used to treat autoimmune diseases such as multiple sclerosis.”
Although further investigations are needed to understand how to precisely modulate circadian rhythm or time-of-the-day cues for beneficial immunity, the findings in this article serve well to remind us the importance of ‘keeping the time’ when dealing with the immune system.
Research Lecturer in the Department of Molecular and Cellular Therapeutics at RCSI, Dr Annie Curtis, said: “Our study also shows how disruption of our body clocks, which is quite common now given our 24/7 lifestyle and erratic eating and sleeping patterns, may have an impact on autoimmune conditions.”
“We are really beginning to uncover exactly how important our body clocks are for health and wellbeing.”
Source: Thomas Deane – TCD
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Original Research: Full open access research for “Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease” by Caroline E. Sutton, Conor M. Finlay, Mathilde Raverdeau, James O. Early, Joseph DeCourcey, Zbigniew Zaslona, Luke A. J. O’Neill, Kingston H. G. Mills & Annie M. Curtis in Nature Communications. Published online December 12 2017 doi:10.1038/s41467-017-02111-0
[cbtabs][cbtab title=”MLA”]TCD “Time of Day Affects Severity of Autoimmune Disease.” NeuroscienceNews. NeuroscienceNews, 12 December 2017.
<https://neurosciencenews.com/time-autoimmune-disease-8169/>.[/cbtab][cbtab title=”APA”]TCD (2017, December 12). Time of Day Affects Severity of Autoimmune Disease. NeuroscienceNews. Retrieved December 12, 2017 from https://neurosciencenews.com/time-autoimmune-disease-8169/[/cbtab][cbtab title=”Chicago”]TCD “Time of Day Affects Severity of Autoimmune Disease.” https://neurosciencenews.com/time-autoimmune-disease-8169/ (accessed December 12, 2017).[/cbtab][/cbtabs]
Abstract
Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease
The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown. Here we show that BMAL1 and time-of-day regulate the accumulation and activation of various immune cells in a CNS autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). In myeloid cells, BMAL1 maintains anti-inflammatory responses and reduces T cell polarization. Loss of myeloid BMAL1 or midday immunizations to induce EAE create an inflammatory environment in the CNS through expansion and infiltration of IL-1β-secreting CD11b+Ly6Chi monocytes, resulting in increased pathogenic IL-17+/IFN-γ+ T cells. These findings demonstrate the importance of the molecular clock in modulating innate and adaptive immune crosstalk under autoimmune conditions.
“Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease” by Caroline E. Sutton, Conor M. Finlay, Mathilde Raverdeau, James O. Early, Joseph DeCourcey, Zbigniew Zaslona, Luke A. J. O’Neill, Kingston H. G. Mills & Annie M. Curtis in Nature Communications. Published online December 12 2017 doi:10.1038/s41467-017-02111-0
