Influence of circadian clocks on adaptive immunity and vaccination responses

Ince, Louise Madeleine; Barnoud, Coline; Lutes, Lydia Kay; Pick, Robert; Wang, Chen; Sinturel, Flore; Chen, Chien-Sin; de Juan, Alba; Weber, Jasmin; Holtkamp, Stephan J.; Hergenhan, Sophia Martina; Geddes-McAlister, Jennifer; Ebner, Stefan; Fontannaz, Paola; Meyer, Benjamin; Vono, Maria; Jemelin, Stéphane; Dibner, Charna; Siegrist, Claire-Anne; Meissner, Felix; Graw, Frederik; Scheiermann, Christoph (2023): Influence of circadian clocks on adaptive immunity and vaccination responses. Nature Communications, 14 (1). ISSN 2041-1723

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.

• Doc-Type: Article (LMU)
• Organisational unit (Faculties): 07 Medicine
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892