Body’s Biological Clock and Time of Day Affects Immune Cells, Mouse Study Shows

Researchers further explored how our internal biological clock — known as circadian rhythm — influences immune system responses. Disruptions to that rhythm are associated with immune diseases like multiple sclerosis (MS), although in ways not fully understood and, the study suggests, may affect response to treatment.

A natural 24-hour cycle that exists in every animal and plant, the circadian rhythm is known to regulate all physiological processes. Maintaining a healthy body clock is increasingly recognized as a key step for good health, and studies have shown that people with a disrupted internal clock — such as night-shift workers — have a higher incidence of diseases like MS.

Researchers at the Trinity Biomedical Sciences Institute, Dublin, and the Royal College of Surgeons Ireland (RCSI) used a mouse model of human MS — the experimental autoimmune encephalomyelitis (EAE) model – and showed that the time-of-day regulates the activation of several of the animals’ immune cells, .

Their study “Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease” was published in the journal Nature Communications.

They found that a gene called BMAL1 — a master regulator of the circadian clock — senses and acts in concert with the time of the day to suppress inflammation. Loss of BMAL1 or inducing EAE at midday (instead of midnight, for instance) was seen to lead to an enhanced inflammatory environment in the central nervous system and, subsequently, more severe disease progression in the mice.

“We found that the course of disease was significantly more severe in wild-type mice immunized at ZT6  … equating to middle of daylight hours, compared with mice immunized at ZT18,” or the equivalent of nighttime hours, the researchers wrote.

“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,” Kingston Mills, the study’s co-lead researcher and a professor of Experimental Immunology at Trinity, said in a press release.

“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,” Mills added.

A better understanding of how to modulate the circadian rhythm and time-of-the-day cues may help design strategies that work to modulate the immune system.

“Collectively, our findings demonstrate that the myeloid molecular clock and circadian rhythms can influence the development of autoimmune disease. Bmal1 expression and a functional molecular clock in myeloid lineage cells appears to regulate these temporal variations, yielding a less pro-inflammatory environment overall,” the researchers concluded.

“Our data provide mechanistic insights into how time-of-day and clock disruption in myeloid cells impacts on autoimmunity thus providing opportunities to enhance circadian function or time-of-day drug-targeting strategies to alleviate autoimmune disease.”