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Cited by 843Circadian rhythm and melatoninSleep and Work-Related FatigueImmune Response and Inflammation

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

A circadian clock in macrophages controls inflammatory immune responses

Open access
Keller, Maren, Mazuch, Jeannine, Abraham, Ute, Eom, Gina D., Herzog, Erik D., Volk, Hans-Dieter, Kramer, Achim, Maier, Bert·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0906361106PMC PMC2795539
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Abstract

Time of day-dependent variations of immune system parameters are ubiquitous phenomena in immunology. The circadian clock has been attributed with coordinating these variations on multiple levels; however, their molecular basis is little understood. Here, we systematically investigated the link between the circadian clock and rhythmic immune functions. We show that spleen, lymph nodes, and peritoneal macrophages of mice contain intrinsic circadian clockworks that operate autonomously even ex vivo. These clocks regulate circadian rhythms in inflammatory innate immune functions: Isolated spleen cells stimulated with bacterial endotoxin at different circadian times display circadian rhythms in TNF-α and IL-6 secretion. Interestingly, we found that these rhythms are not driven by systemic glucocorticoid variations nor are they due to the detected circadian fluctuation in the cellular constitution of the spleen. Rather, a local circadian clock operative in splenic macrophages likely governs these oscillations as indicated by endotoxin stimulation experiments in rhythmic primary cell cultures. On the molecular level, we show that >8% of the macrophage transcriptome oscillates in a circadian fashion, including many important regulators for pathogen recognition and cytokine secretion. As such, understanding the cross-talk between the circadian clock and the immune system provides insights into the timing mechanism of physiological and pathophysiological immune functions.

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Metadata

Authors
Keller, M., Mazuch, J., Abraham, U., Eom, G. D., Herzog, E. D., Volk, H.-D., Kramer, A., & Maier, B.
Affiliations
  • Laboratory of Chronobiology, Institute for Medical Immunology, and Research Center ImmunoSciences and
  • Washington University in St. Louis (US)
  • Charité – Universitätsmedizin Berlin (DE)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-12-15
Volume
106
Issue
50
Pages
21407-21412
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0906361106
PMC
PMC2795539
OpenAlex
W2090209293
Cited by
843
References
44
Citations by year
2026: 58 · 2025: 64 · 2024: 44 · 2023: 55 · 2022: 57 · 2021: 80 · 2020: 71 · 2019: 59 · 2018: 48 · 2017: 56 · 2016: 51 · 2015: 53 · 2014: 47 · 2013: 42 · 2012: 22
FWCI
8.38
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • European Commission
  • Deutsche Forschungsgemeinschaft
  • National Institutes of Health
  • National Institute of Mental Health (R01MH063104, MH 63104)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
circadian clock, macrophages, innate immunity, inflammatory immune response, circadian rhythm, endotoxin stimulation, TNF-α, interleukin-6, cytokine production, splenic macrophages, glucocorticoids, pathogen recognition
MeSH terms
Animals, Circadian Rhythm, Gene Expression Regulation, Immunity, Innate, Inflammation, Lipopolysaccharides, Lymph Nodes, Macrophages, RNA, Messenger, Spleen, Tumor Necrosis Factor-alpha, Interleukin-6, Macrophages, Peritoneal, Mice

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