Body clock discovery gives clues to how we fight disease

18 May 2015

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Body clock discovery gives clues to how we fight disease

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Scientists have discovered a strange approach that our immune system takes to combatting illness, overriding our body clock to focus on unwanted bacteria for a short space of time.

Studying our body’s white blood cells (macrophages), researchers at Trinity College Dublin (TCD) and the University of Pennsylvania realised that our standard body clock is overridden when unwanted bacteria is uncovered.

Explaining the mechanism, senior research fellow in biochemistry and immunology at TCD, Dr Annie Curtis, who is a lead author of the paper, said: “It’s as if an infection causes the alarm in a macrophage clock to go off.”

The circadian system is our body’s physiological clock. From a basic premise, it acts according to the time of day. For example, our body attacks illness far more strongly during the night, and we have evolved to be far more active during the day.

This discovery, which shows how our immune system undermines this reflex when it feels the need, helps us better understand our body’s decision making.

“Without understanding that we’ll never get to the next point, where we can make educated decisions and design therapies for patients’ care where the circadian clock may be included in the mix.”

What essentially happens, according to this study, is the white blood cells act as patrolmen. They frequent the body looking for any unwanted threats and, upon finding something, stop the body clock.

“They’re spoken about as the scavenger cells,” she says. “They scour the body and if there’s anything that looks odd that they comes across they can eat it up, chew it and destroy it.”

Within an activated macrophage, miR-155 stops the clock by targeting the main clock protein, BMAL1. (Image credit: M. Haneklaus, 2015)

Within an activated macrophage, miR-155 stops the clock by targeting the main clock protein, BMAL1. (Image credit: M. Haneklaus, 2015)

Within an activated macrophage, miR-155 stops the clock by targeting the main clock protein, BMAL1. (Image credit: M. Haneklaus, 2015)

The complex mechanism involves a factor called miR-155, which destroys a key cog in the clock’s mechanism called BMAL1. This allows the macrophage to make a number of inflammatory proteins that effectively wake up and activate the immune system.

Our bodies are deciding that, regardless of the time of day, they need to attack the illness immediately. Yet what if this, too, happens better at night?

“There may be times such as during an acute infection where it’s advantageous for the immune system to use miR-155 to stop the macrophage clock and allow the body to clear the infection,” said Professor Garret FitzGerald, from the University of Pennsylvania, who is a joint senior author.

However, he added: “When inflammation is present for long periods of time, as is the case for patients with a chronic disease like rheumatoid arthritis, this constant targeting of the clock may actually worsen disease.”

“Think of cancer immunotherapy,” says Curtis. “These are often really expensive new medicines coming on board. Ipilimumab, for example, is an antibody that masks the ‘off switch’ on the immune system.

Immunotherapy, basically, is given to people with certain cancers so that a certain type of cell in the immune system can go and attack the tumour. And Curtis thinks these types of “ground-breaking” medicines are the future of cancer treatment.

She notes that there’s “nothing better than the immune system” when treating illness, so harnessing its power would be big.

“But thinking of that, it’s given to patients at a certain time of day. If there was a better time to give that treatment, when our immune system is more active, and you put it on top of that and you have a better chance.”

The study was published this week in leading international peer-reviewed journal Proceedings of the National Academy of Sciences USA.

Clock image, via Shutterstock

Gordon Hunt is senior communications and context executive at NDRC. He previously worked as a journalist with Silicon Republic.

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