Researchers in Ireland report that immune responses and regulation of autoimmunity are affected by the time of the day when the immune response is activated. 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, say the scientists who published their study (“Loss of the Molecular Clock in Myeloid Cells Exacerbates T Cell-Mediated CNS Autoimmune Disease”) in Nature Communications.
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 analog of multiple sclerosis in mice.
“Loss of myeloid BMAL1 or midday immunizations to induce EAE [experimental autoimmmune encephalomyelitis] 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,” say the investigators. “These findings demonstrate the importance of the molecular clock in modulating innate and adaptive immune crosstalk under autoimmune conditions.”
“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,”says Kingston Mills, Ph.D., professor of experimental immunology at Trinity College, Dublin. “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, our findings serve well to remind us the importance of “keeping the time” when dealing with the immune system, he adds.
“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,” notes Annie Curtis, Ph.D., of the Royal College of Surgeons Ireland. “We are really beginning to uncover exactly how important our body clocks are for health and well-being.”