Researchers at RCSI University of Medicine and Health Sciences have demonstrated in a new mouse study how our body clock influences our immune response to vaccines. The findings may help improve the design and timing of the administration of future vaccines to maximize effectiveness.

The findings are published in Nature Communications in an article titled, “The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing.”

“Dendritic cells play a key role in processing and presenting antigens to naïve T cells to prime adaptive immunity,” wrote the researchers. “Circadian rhythms are known to regulate many aspects of immunity; however, the role of circadian rhythms in dendritic cell function is still unclear. Here, we show greater T-cell responses when mice are immunized in the middle of their rest versus their active phase. We find a circadian rhythm in antigen processing that correlates with rhythms in both mitochondrial morphology and metabolism, dependent on the molecular clock gene, Bmal1.”

Research author Annie Curtis, PhD, professor at the School of Pharmacy and Biomolecular Sciences at RCSI said: “Our discovery has shed light on a crucial aspect of our body’s response to vaccination and highlights the importance of circadian rhythms in immunity. We can apply this understanding in vaccine development to ensure we receive the maximum benefits from vaccination.”

“Using Mdivi-1, a compound that promotes mitochondrial fusion, we are able to rescue the circadian deficit in antigen processing and mechanistically link mitochondrial morphology and antigen processing,” wrote the researchers. “Furthermore, we find that circadian changes in mitochondrial Ca2+ are central to the circadian regulation of antigen processing. Our results indicate that rhythmic changes in mitochondrial calcium, which are associated with changes in mitochondrial morphology, regulate antigen processing.”

The circadian clock within dendritic cells is controlling whether mitochondria form one of two shapes either long strings, “networked,” or broken into small punctate pieces. It is within the networked formation that vaccination is most effective as dendritic cells have a better ability to break up the vaccine into small pieces for interaction with our immune cells (T cells).

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