Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease, 2017, Mills, Curtis et al

Andy · Dec 12, 2017

Abstract

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.
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Open access at https://www.nature.com/articles/s41467-017-02111-0

Andy · Dec 12, 2017

Article based on this paper

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.
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http://neurosciencenews.com/time-autoimmune-disease-8169/

Sly Saint · Oct 12, 2018

watched Horizon last night

"
Body Clock: What Makes Us Tick?
Horizon 2018
We all have a biological clock ticking away inside us that governs our daily rhythms. This affects our health as much as our diet and whether we exercise. So what can we do to manage this internal clock better?

To find out, evolutionary biologist Ella Al-Shamahi locks former commando Aldo Kane in an abandoned nuclear bunker with no way of telling the time - for ten days. Monitored around the clock by a team of scientists, he carries out a barrage of tests to uncover exactly what makes our body clock tick.

Above ground, Ella meets two time-starved couples to test the latest thinking on how we can manage our body clocks better. In trying to improve their sleep, and their lives, she uncovers practical advice that we can all take on board. Studies on shift workers show that regularly disrupting our sleep makes us more at risk of diabetes, heart disease and even cancer. So getting to grips with our biological clock couldn't be more important."

But the most interesting bit was the interview with one of the original researchers (Professor Jeffrey Hall Chronobiologist) and the explanation of how the Period gene works (21.30), not just in fruit flies but also in humans.

https://www.bbc.co.uk/iplayer/episode/b0bn5ys4/horizon-2018-9-body-clock-what-makes-us-tick

for real scientific stuff:
Circadian rhythms in mitochondrial respiration.
https://www.ncbi.nlm.nih.gov/pubmed/29378772

and very complicated stuff:
PER1 period circadian regulator 1 Homo sapiens (human)
https://www.ncbi.nlm.nih.gov/gene/5187

would be interesting to see if there is any real disruption of the circadian clock at the cellular level (as opposed to observing things at different times of the day) in pwME.

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Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease, 2017, Mills, Curtis et al

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