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Synchronization of the Normal Human Peripheral Immune System: A Comprehensive Circadian Systems Immunology Analysis

Research output: Contribution to journalArticle

Craig A. Beam, Clive Wasserfall, Alyssa Woodwyk, McKenzie K. Akers, Heather Rauch, Thomas Blok, Patrice Mason, Duncan Vos, Daniel Perry, Todd Brusko, Mark Peakman, Mark Atkinson

Original languageEnglish
Article number672
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

King's Authors

Abstract

In this study, we sought to fill an important gap in fundamental immunology research by conducting a comprehensive systems immunology analysis of daily variation in the normal human peripheral immune system. Although variation due to circadian rhythmicity was not a significant source of variation in daily B-cell levels or any CD4+ functional subset, it accounted for more than 25% of CD4+ regulatory T-cell variation and over 50% of CD8+ central memory variation. Circadian rhythmicity demonstrated phase alignment within functional phenotypes. In addition, we observed that previously-described mechanistic relationships can also appear in the peripheral system as phase shifting in rhythmic patterns. We identified a set of immune factors which are ubiquitously correlated with other factors and further analysis also identified a tightly-correlated “core” set whose relational structure persisted after analytically removing circadian-related variation. This core set consisted of CD8+ and its subpopulations and the NK population. In sum, the peripheral immune system can be conceptualized as a dynamic, interconnected wave-field repeating its pattern on a daily basis. Our data provide a comprehensive inventory of synchronization and correlation within this wave-field and we encourage use of our data to discover unknown mechanistic relationships which can then be tested in the laboratory.

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