Immune Cells Exhibit Faster and More Robust Activation in the Morning

New research from RCSI University of Medicine and Health Sciences has explained how the body’s internal clock influences the inflammatory process of the immune system. The findings describe how immune cells, called macrophages, work differently at various times of the day and could pave the way for time-targeted treatments for inflammatory diseases such as arthritis.

The researchers explored the link between the immune system and the body’s circadian rhythms often referred to as the body clock. Macrophages, immune cells that detect and respond to harmful substances, are able to trigger inflammation as a defence mechanism by assembling large complexes known as inflammasomes. Inflammasomes could be compared to ‘smoke detectors’ that will then alert the immune system of danger.

Activation of an inflammasome called NLRP3 was not found to be constant throughout the day but was regulated by the body’s 24-hour circadian clock. This daily rhythm determines when macrophages are most efficient at detecting threats and when their energy levels peak to mount a response. The research also highlights a key role for mitochondria, the cell’s energy producers, in driving these daily changes in immune activity.

“When macrophages ‘think’ it’s morning, their inflammasome activation is quicker and more robust,” explained Professor Annie Curtis, principal investigator for the study at RCSI School of Pharmacy and Biomolecular Sciences. “This means the immune response is heightened during the early part of the day, a time when we are awake and more likely to encounter environmental challenges, such as injuries or infections.”

The study has significant implications for understanding and treating inflammatory diseases, such as arthritis, where overactive inflammasomes play a key role. Symptoms of such diseases often worsen in the morning, something this research may help explain.

“With these findings, there’s potential to refine treatments for inflammatory conditions,” said Dr James O’Siorain, lead author of the study. “For instance, new therapies targeting inflammasomes could be more effective if administered at specific times of the day when macrophage activity peaks.”

Reference: O’Siorain JR, Cox SL, Payet C, et al. Time-of-day control of mitochondria regulates NLRP3 inflammasome activation in macrophages. The FASEB Journal. 2024;38(24):e70235. doi: 10.1096/fj.202400508RR

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