Royal College of Surgeons in Ireland
Cervantes-Silva et al. - 2022 - The circadian clock influences T cell responses to.pdf (3.91 MB)

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

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posted on 2023-03-16, 08:02 authored by Mariana P Cervantes-Silva, Richard G Carroll, Mieszko M Wilk, Diana Moreira, Cloe PayetCloe Payet, James O'SiorainJames O'Siorain, Shannon CoxShannon Cox, Lauren FaganLauren Fagan, Paula KlavinaPaula Klavina, Yan HeYan He, Tabea Drewinski, Alan McGinley, Sharleen M Buel, George A Timmons, James O Early, Roger PrestonRoger Preston, Jennifer M Hurley, David K Finlay, Ingmar SchoenIngmar Schoen, F Javier Sánchez-García, Kingston HG Mills, Annie CurtisAnnie Curtis
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.


Science Foundation Ireland through a Career Development Award (17/CDA/4688)

Irish Research Council through a Laureate Award (IRCLA/2017/110)

RCSI Strategic Academic Recruitment Program (StAR)

Conacyt grant (CVU440823)

Science Foundation Ireland Investigator Award (16/IA/4468)

European Research Council Consolidator Award (ERC-CoG_771419)



The original article is available at

Published Citation

Cervantes-Silva MP. Et al. The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing. Nat Commun. 2022;13(1):7217.

Publication Date

5 December 2022

PubMed ID



  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences
  • Tissue Engineering Research Group (TERG)

Research Area

  • Vascular Biology
  • Biomaterials and Regenerative Medicine
  • Immunity, Infection and Inflammation
  • Health Professions Education


Nature Pub. Group


  • Published Version (Version of Record)