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Publication : The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing.

First Author  Cervantes-Silva MP Year  2022
Journal  Nat Commun Volume  13
Issue  1 Pages  7217
PubMed ID  36470865 Mgi Jnum  J:331999
Mgi Id  MGI:7407675 Doi  10.1038/s41467-022-34897-z
Citation  Cervantes-Silva MP, et al. (2022) The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing. Nat Commun 13(1):7217
abstractText  Dendritic cells play a key role in processing and presenting antigens to naive T cells to prime adaptive immunity. 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 immunised 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. 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. Furthermore, we find that circadian changes in mitochondrial Ca(2+) 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.
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