Influence of circadian clocks on adaptive immunity and vaccination responses.

Jennifer Geddes-McAlister, Christoph Scheiermann, Frederik Graw, Felix Meissner, Claire-Anne Siegrist, Charna Dibner, Stéphane Jemelin, Maria Vono, Benjamin Meyer, Paola Fontannaz, Stefan Ebner, Louise Madeleine Ince, Sophia Martina Hergenhan, Stephan J Holtkamp, Jasmin Weber, Alba de Juan, Chien-Sin Chen, Flore Sinturel, Chen Wang, Robert Pick, Lydia Kay Lutes, Coline Barnoud

Journal: Nature communications 2023;14(1):476

PMID: 36717561

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Abstract

The adaptive immune response is under circadian control, yet, why adaptive immune reactions continue to exhibit circadian changes over long periods of time is unknown. Using a combination of experimental and mathematical modeling approaches, we show here that dendritic cells migrate from the skin to the draining lymph node in a time-of-day-dependent manner, which provides an enhanced likelihood for functional interactions with T cells. Rhythmic expression of TNF in the draining lymph node enhances BMAL1-controlled ICAM-1 expression in high endothelial venules, resulting in lymphocyte infiltration and lymph node expansion. Lymph node cellularity continues to be different for weeks after the initial time-of-day-dependent challenge, which governs the immune response to vaccinations directed against Hepatitis A virus as well as SARS-CoV-2. In this work, we present a mechanistic understanding of the time-of-day dependent development and maintenance of an adaptive immune response, providing a strategy for using time-of-day to optimize vaccination regimes.

Address: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Division of Pharmacology & Toxicology, College of Pharmacy, University of Texas at Austin, Austin, TX, USA.; Department of Medicine, Division of Endocrinology, Diabetes, Nutrition and Patient Education, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, Geneva, Switzerland.; Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University Munich, BioMedical Centre, Planegg-Martinsried, Germany.; Experimental Systems Immunology, Max Planck Institute of Biochemistry, Martinsried, Germany.; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.; Systems Immunology and Proteomics, Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.; World Health Organization Collaborating Center for Vaccine Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; BioQuant - Center for Quantitative Biology, Heidelberg University, Heidelberg, Germany.; Interdisciplinary Center for Scientific Computing, Heidelberg University, Heidelberg, Germany.; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. [email protected].; Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva, Geneva, Switzerland. [email protected].; Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University Munich, BioMedical Centre, Planegg-Martinsried, Germany. [email protected].; Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. [email protected].

DOI: 10.1038/s41467-023-35979-2

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MeSH Terms: Humans, Circadian Clocks, COVID-19, SARS-CoV-2, Adaptive Immunity, Vaccination, Lymph Nodes