biostudies-literatureCervantes-Silva MPEuropean Research CouncilScience Foundation IrelandNIGMS NIH HHS7217https://www.ebi.ac.uk/biostudies/studies/S-EPMC9722918biostudies-literatureUnknown13(1)Dendritic cells play a key role in processing and presenting antigens to naïve 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 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.Nature communicationsThe circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing.PMC972291877141917/CDA/4688R35 GM128687IRCLA/2017/11016/IA/4468O'Siorain JRMills KHGWilk MMBuel SMCarroll RGTimmons GACervantes-Silva MPSchoen IDrewinski THurley JMCurtis AMCox SLMcGinley AKlavina PAMoreira DPreston RJSHe YFinlay DKJavier Sanchez-Garcia FFagan LEEarly JOPayet CAfalseThe 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. 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 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.2022-01-01T00:00:00Z2022 Dec2025-04-22T00:39:42.187Z2025-04-05T19:36:00.878ZS-EPMC97229183647086510.1038/s41467-022-34897-z