CoChat
Sign Up
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
Open this paper in CoChat — free account

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.0906361106

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Cited by

Sorted by citations

  • About Sleep's Role in Memory

    Rasch, B., & Born, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00032.2012 · Cited by 2,783

    “In combination, these data support the view that sleep favors an accumulation of T cells in lymph nodes, and there might be a parallel effect on APC migration (307, 627).”
    BackgroundResult

  • Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis

    Thaiss, C. A., Zeevi, D., Levy, M., Zilberman-Schapira, G., Suez, J., Tengeler, A. C., Abramson, L., Katz, M. N., Korem, T., Zmora, N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.048 · Cited by 1,449

    “…many biological processes, ranging from metabolism and behavior to immunity, and helps to synchronize these processes to diurnal fluctuations in environmental conditions (Asher et al., 2010; Gerhart-Hines et al., 2013; Keller et al., 2009; Nguyen et al., 2013; Silver et al., 2012; Yu et al., 2013).”
    Background

  • Sleep and immune function

    Besedovsky, L., Lange, T., & Born, J. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-1044-0 · Cited by 1,153

    “Peaks of pro-inflammatory and/or Th1 cytokines during the rest period have been observed, often during the early slow wave sleep (SWS)-dominated portion of sleep, in humans as well as in animals on the mRNA and protein level in different tissues including the brain [52, 69], adipose tissue [52] and lymph nodes [41], b…”
    Background

  • Circadian control of the immune system

    Scheiermann, C., Kunisaki, Y., & Frenette, P. S. (2013) · Nature Reviews Immunology · doi:10.1038/nri3386 · Cited by 1,135

  • The human stress response

    Russell, G., & Lightman, S. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0228-0 · Cited by 1,032

See all 843

Related

See all

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review