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

Author

Listed:
  • Mariana P. Cervantes-Silva

    (Royal College of Surgeons in Ireland RCSI)

  • Richard G. Carroll

    (Royal College of Surgeons in Ireland RCSI)

  • Mieszko M. Wilk

    (Trinity College Dublin
    Jagiellonian University)

  • Diana Moreira

    (Trinity College Dublin)

  • Cloe A. Payet

    (Royal College of Surgeons in Ireland RCSI)

  • James R. O’Siorain

    (Royal College of Surgeons in Ireland RCSI)

  • Shannon L. Cox

    (Royal College of Surgeons in Ireland RCSI)

  • Lauren E. Fagan

    (Royal College of Surgeons in Ireland RCSI
    Royal College of Surgeons in Ireland RCSI)

  • Paula A. Klavina

    (Royal College of Surgeons in Ireland RCSI
    Royal College of Surgeons in Ireland RCSI)

  • Yan He

    (Royal College of Surgeons in Ireland RCSI
    Soochow University)

  • Tabea Drewinski

    (Royal College of Surgeons in Ireland RCSI)

  • Alan McGinley

    (Royal College of Surgeons in Ireland RCSI)

  • Sharleen M. Buel

    (Rensselaer Polytechnic Institute)

  • George A. Timmons

    (Royal College of Surgeons in Ireland RCSI)

  • James O. Early

    (Royal College of Surgeons in Ireland RCSI
    Royal College of Surgeons in Ireland RCSI)

  • Roger J. S. Preston

    (Royal College of Surgeons in Ireland RCSI)

  • Jennifer M. Hurley

    (Rensselaer Polytechnic Institute)

  • David K. Finlay

    (Trinity College Dublin)

  • Ingmar Schoen

    (Royal College of Surgeons in Ireland RCSI)

  • F. Javier Sánchez-García

    (Instituto Politécnico Nacional)

  • Kingston H. G. Mills

    (Trinity College Dublin)

  • Annie M. Curtis

    (Royal College of Surgeons in Ireland RCSI
    Trinity College Dublin
    Royal College of Surgeons in Ireland RCSI
    Royal College of Surgeons in Ireland RCSI)

Abstract

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.

Suggested Citation

  • Mariana P. Cervantes-Silva & Richard G. Carroll & Mieszko M. Wilk & Diana Moreira & Cloe A. Payet & James R. O’Siorain & Shannon L. Cox & Lauren E. Fagan & Paula A. Klavina & Yan He & Tabea Drewinski , 2022. "The circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34897-z
    DOI: 10.1038/s41467-022-34897-z
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    References listed on IDEAS

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    1. Joshua M. Baughman & Fabiana Perocchi & Hany S. Girgis & Molly Plovanich & Casey A. Belcher-Timme & Yasemin Sancak & X. Robert Bao & Laura Strittmatter & Olga Goldberger & Roman L. Bogorad & Victor Ko, 2011. "Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter," Nature, Nature, vol. 476(7360), pages 341-345, August.
    2. Diego De Stefani & Anna Raffaello & Enrico Teardo & Ildikò Szabò & Rosario Rizzuto, 2011. "A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter," Nature, Nature, vol. 476(7360), pages 336-340, August.
    3. Simon J. Lawless & Nidhi Kedia-Mehta & Jessica F. Walls & Ryan McGarrigle & Orla Convery & Linda V. Sinclair & Maria N. Navarro & James Murray & David K. Finlay, 2017. "Glucose represses dendritic cell-induced T cell responses," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
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