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

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A circadian clock in macrophages controls inflammatory immune responses

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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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Lu, Y.-C., Yeh, W.-C., & Ohashi, P. S. (2008) · Cytokine · doi:10.1016/j.cyto.2008.01.006 · Cited by 3,301
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Yamazaki, S., Numano, R., Abe, M., Hida, A., Takahashi, R.-I., Ueda, M., Block, G. D., Sakaki, Y., Menaker, M., & Tei, H. (2000) · Science · doi:10.1126/science.288.5466.682 · Cited by 1,907
Resetting of circadian time in peripheral tissues by glucocorticoid signaling
Balsalobre, A., Brown, S. A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H. M., Schütz, G., & Schibler, U. (2000) · Science · doi:10.1126/science.289.5488.2344 · Cited by 1,859
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Ralph, M. R., Foster, R. G., Davis, F. C., & Menaker, M. (1990) · Science · doi:10.1126/science.2305266 · Cited by 1,853
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Takahashi, J. S., Hong, H.-K., Ko, C. H., & McDearmon, E. L. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2430 · Cited by 1,611
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Méndez‐Ferrer, S., Lucas, D., Battista, M., & Frenette, P. S. (2008) · Nature · doi:10.1038/nature06685 · Cited by 1,310
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Additional file 1 of Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques
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Additional file 3 of Pharmacological activation of rev-erbα suppresses LPS-induced macrophage M1 polarization and prevents pregnancy loss
Cui, L., Xu, F., Wang, S. N., Li, X., Lin, H., Ding, Y., & Du, M. (2021) · Figshare · doi:10.6084/m9.figshare.15179281
Additional file 4 of Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques
Shen, Y., Xu, L.-R., Tang, X., Lin, C.-P., Yan, D., Xue, S., Qian, R.-Z., & Guo, D.-Q. (2021) · Figshare · doi:10.6084/m9.figshare.14728264
Additional file 2 of Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques
Shen, Y., Xu, L.-R., Tang, X., Lin, C.-P., Yan, D., Xue, S., Qian, R.-Z., & Guo, D.-Q. (2021) · Figshare · doi:10.6084/m9.figshare.14728258
Additional file 2 of Pharmacological activation of rev-erbα suppresses LPS-induced macrophage M1 polarization and prevents pregnancy loss
Cui, L., Xu, F., Wang, S. N., Li, X., Lin, H., Ding, Y., & Du, M. (2021) · Figshare · doi:10.6084/m9.figshare.15179278
Additional file 6 of Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques
Shen, Y., Xu, L.-R., Tang, X., Lin, C.-P., Yan, D., Xue, S., Qian, R.-Z., & Guo, D.-Q. (2021) · Figshare · doi:10.6084/m9.figshare.14728270
Additional file 5 of Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques
Shen, Y., Xu, L.-R., Tang, X., Lin, C.-P., Yan, D., Xue, S., Qian, R.-Z., & Guo, D.-Q. (2021) · Figshare · doi:10.6084/m9.figshare.14728267
Additional file 2 of Time of day as a critical variable in biology
Nelson, R. J., Bumgarner, J. R., Liu, J. A., Love, J. A., Meléndez‐Fernández, O. H., Becker‐Krail, D. D., Walker, W. H., Walton, J. C., DeVries, A. C., & Prendergast, B. J. (2022) · Figshare · doi:10.6084/m9.figshare.20076777
“Remote and partial clocks expand the circadian neuronal network, driving widespread molecular rhythmicity in Drosophila ”Preprint
Patop, I. L., Anduaga, A. M., Rashkover, T., Morales, J., Brownstein, N., Carmona, C. R., Bussi, I. L., Ceriani, M. F., Kurmangaliyev, Y. Z., & Kadener, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.23.696232
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“19,21 22-24 Moreover, circadian regulation of immunity is also evident beyond the monocyte/macrophage lineages, such as B cells, T cells, dendritic cells, and neutrophils.”
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Araujo, M. M. (2026) · Biosystems · doi:10.1016/j.biosystems.2026.105713
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Loss of daily phase relations identified by multiomic analyses in acute pancreatitis
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“This finding was replicated by Keller et al., who showed a large difference in circulating macrophage numbers depending on the time of day when mice were injected with LPS [47].”
Circadian synchronization between diet and gut microbiota in modulating host's health
Ma, J., Zhen, Y., Weng, Y., Lin, J., Zhang, C., Zhong, Y., Zhou, J., & Wang, M. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2647602 · Cited by 1
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“Diurnal changes in immune cell numbers in blood and tissues [45], cytokine production under pathogen stimulation [8], and immune cell effector functions [13] suggest that both the innate and adaptive immune systems in peripheral tissues are regulated by the circadian system.”
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Leclère, P. S. (2019) · theses.fr (ABES) · doi:10.70675/7a3e667czbdf7z4068zbadfzd850044a706a
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Daher, M. (2019) · theses.fr (ABES) · doi:10.70675/bdcede14z3bf1z4c2ez937czbcf99935b333
Circadian clocks and cancer : The implication of BMAL1 (brain and muscle Arnt-like protein-1) in colorectal and breast carcinoma development and treatment
Zhang, Y. (2019) · theses.fr (ABES) · doi:10.70675/f9bc8234z71f7z4d14z88f2zf9c8dcdf114f · Cited by 1
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de Jenlis, A. B. (2018) · theses.fr (ABES) · doi:10.70675/780e0675z5515z4d02zaa37z88eba9598297

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: Abraham, Ute
Herzog, Erik D.
Volk, Hans-Dieter
Kramer, Achim
Maier, Bert
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: green
www.ncbi.nlm.nih.gov
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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A circadian clock in macrophages controls inflammatory immune responses

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