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A circadian clock in macrophages controls inflammatory immune responses
Open accessAbstract
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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“Conversely, there are hints that owing to an overshooting proinflammatory cytokine response, the immediate defense of antigen is impaired during sleep, particularly during SWS (508,627,693,779).”
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“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).”
From About Sleep's Role in Memory (2013) · cites this paper as [627]
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The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids
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Dysregulation of inflammatory responses by chronic circadian disruption
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The role of interleukin-6 signaling in nervous tissue
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BackgroundMolecular regulations of circadian rhythm and implications for physiology and diseases
Fagiani, F., Marino, D. D., Romagnoli, A., Travelli, C., Voltan, D., Mannelli, L. D. C., Racchi, M., Govoni, S. M., & Lanni, C. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00899-y · Cited by 518
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Circadian Clocks in the Immune System
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Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines
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MethodCore circadian protein CLOCK is a positive regulator of NF-κB–mediated transcription
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BackgroundResultInfluentialCrosstalk between the circadian clock circuitry and the immune system
Cermakian, N., Lange, T., Golombek, D., Sarkar, D., Nakao, A., Shibata, S., & Mazzoccoli, G. (2013) · Chronobiology International · doi:10.3109/07420528.2013.782315 · Cited by 279
“…2008; Mazzoccoli et al., 2011d; Teboul et al., 2005) and controls the expression of transcription factors involved in immune cell differentiation and functioning, including signal transducer and activator of transcription 3 and 5 (STAT3, STAT5) and NF-kB (Bozek et al., 2009; Keller et al., 2009).”
BackgroundThe role of non-resolving inflammation in atherosclerosis
Kasikara, C., Doran, A. C., Cai, B., & Tabas, I. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97950 · Cited by 266
High-accuracy determination of internal circadian time from a single blood sample
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“We chose to use peripheral blood monocytes as source material for gene expression profiling, because (a) blood is an easily accessible source of human cells and (b) monocytes constitute a homogenous blood cell population and have been shown to possess a high-amplitude circadian clock (24, 25) in contrast to other PBMC…”
Self-citationCircadian clock regulates the host response to Salmonella
Bellet, M. M., Deriu, E., Liu, J. Z., Grimaldi, B., Blaschitz, C., Zeller, M., Edwards, R. A., Sahar, S., Dandekar, S., Baldi, P., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120636110 · Cited by 260
“Moreover, macrophages have an efficient clock machinery, and LPS-activated pathways in these cells are under tight circadian regulation at multiple levels (3, 4).”
BackgroundCircadian clock protein Rev-erbα regulates neuroinflammation
Griffin, P., Dimitry, J. M., Sheehan, P. W., Lananna, B. V., Guo, C., Robinette, M. L., Hayes, M. E., Cedeño, M. R., Nadarajah, C. J., Ezerskiy, L. A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1812405116 · Cited by 263
Circadian rhythm reprogramming during lung inflammation
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Perfect timing: circadian rhythms, sleep, and immunity — an NIH workshop summary
Haspel, J. A., Anafi, R. C., Brown, M. K., Cermakian, N., Depner, C. M., Desplats, P., Gelman, A. E., Haack, M., Jelić, S., Kim, B., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.131487 · Cited by 261
“Significantly, all lymphoid organs and immune cell types tested to date harbor functional clocks (31, 32).”
BackgroundNeuroinflammation, Sleep, and Circadian Rhythms
Zielinski, M. R., & Gibbons, A. J. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.853096 · Cited by 273
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Circadian timing of metabolism in animal models and humans
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Chronopharmacology: New Insights and Therapeutic Implications
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“For example, the response of T cells to stimulation varies in a circadian fashion (64), and macrophages, in turn, stimulate immune responses in an equally diurnal fashion with their own clocks (65).”
Pourcet, B., Zecchin, M., Ferri, L., Beauchamp, J., Sitaula, S., Billon, C., Delhaye, S., Vanhoutte, J., Mayeuf-Louchart, A., Thorel, Q., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.12.019 · Cited by 232
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“Many genes in the LPS-induced signaling cascade are rhythmically expressed in peritoneal macrophages at steady state, and splenocytes exhibit rhythmic tumor necrosis factor– (TNF-) and interleukin-6 (IL-6) production after LPS challenge (21).”
BackgroundCircadian dysfunction in disease
Bechtold, D. A., Gibbs, J. E., & Loudon, A. S. I. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.01.002 · Cited by 213
Circadian Clocks in Mouse and Human CD4+ T Cells
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“Our results are supported by a previous study showing that in freshly isolated non-stimulated peritoneal mouse macrophages IkBa is under circadian control [14].”
BackgroundResultCircadian Variation of the Response of T Cells to Antigen
Fortier, E. E., Rooney, J., Dardente, H., Hardy, M., Labrecque, N., & Cermakian, N. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1004030 · Cited by 199
“In rodents, susceptibility to lethal doses of the bacterial endotoxin LPS presents a diurnal rhythm (11, 12) and is exacerbated upon circadian disruption (13).”
BackgroundInfluentialTuning the Mammalian Circadian Clock: Robust Synergy of Two Loops
Relógio, A., Westermark, P. O., Wallach, T. E., Schellenberg, K., Kramer, A., & Herzel, H. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002309 · Cited by 207
“Such processes include sleep-awake cycles, memory consolidation [12,13], metabolism of glucose, lipids and drugs [14,15], bone formation [16], hormone regulation, immunity [17], the timing of cell division cycle and the physiological rhythms such as heart rate, blood pressure and body temperature [18].”
BackgroundSelf-citationChrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis
Winter, C., Silvestre-Roig, C., Ortega‐Gómez, A., Lemnitzer, P., Poelman, H., Schumski, A., Winter, J., Drechsler, M. D., de Jong, R., Immler, R., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.002 · Cited by 199
When Rhythms Meet the Blues: Circadian Interactions with the Microbiota-Gut-Brain Axis
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“There is emerging evidence that circadian rhythms govern proinflammatory cytokine gene expression (41, 44, 50).”
BackgroundCircadian nature of immune function
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“Interestingly, the circadian clock was recently implicated in the regulation of inflammatory response [31]; CLOCK deficiency significantly impairs circadian clock function in peripheral organs, thus, CLOCK may be involved in the regulation of skin inflammation through the circadian control of inflammation.”
BackgroundCircadian rhythms: a regulator of gastrointestinal health and dysfunction
Voigt, R. M., Forsyth, C. B., & Keshavarzian, A. (2019) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2019.1595588 · Cited by 193
Nobis, C. C., Laramée, G. D., Kervezee, L., Sousa, D. M. D., Labrecque, N., & Cermakian, N. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905080116 · Cited by 180
“(26) observed a rhythm of the percentage of T cells (using CD90.”
BackgroundCircadian expression of clock genes in mouse macrophages, dendritic cells, and B cells
Silver, A. C., Arjona, A., Hughes, M. E., Nitabach, M. N., & Fikrig, E. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.10.001 · Cited by 181
“3B; Table S3), however, its expression level was highest at the beginning of the subjective day, which is consistent with expression in peritoneal macrophages under DD conditions (Keller et al., 2009).”
BackgroundResultInfluentialde Kivit, S., Tobin, M. C., Forsyth, C. B., Keshavarzian, A., & LANDAY, A. L. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00060 · Cited by 185
The Circadian Clock Controls Immune Checkpoint Pathway in Sepsis
Deng, W., Zhu, S., Zeng, L., Liu, J., Kang, R., Yang, M., Cao, L., Wang, H., Billiar, T. R., Jiang, J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.026 · Cited by 173
“, C-X-C motif chemokine ligand 1, C-C motif chemokine ligand 5, and C-C motif chemokine ligand 2 [CCL2]) were excessively induced by endotoxemia in animals with abnormal circadian rhythms (Castanon-Cervantes et al., 2010; Curtis et al., 2015; García et al., 2015; Gibbs et al., 2012; Hashiramoto et al., 2010; Keller et…”
Zeng, Y., Guo, Z., Wu, M., Chen, F., & Chen, L. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01960-1 · Cited by 197
Molecular Interactions Between Components of the Circadian Clock and the Immune System
Hergenhan, S. M., Holtkamp, S., & Scheiermann, C. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.044 · Cited by 178
Chronic Shift-Lag Alters the Circadian Clock of NK Cells and Promotes Lung Cancer Growth in Rats
Logan, R. W., Zhang, C., Murugan, S., O’Connell, S., Levitt, D., Rosenwasser, A. M., & Sarkar, D. K. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102715 · Cited by 166
“4 software (21, 49) to determine the bestfitting linear harmonic regression with an assumed period of 24 h and with a set at 0.”
BackgroundMethodSpörl, F., Korge, S., Jürchott, K., Wunderskirchner, M., Schellenberg, K., Heins, S., Specht, A., Stoll, C., Klemz, R., Maier, B., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118641109 · Cited by 165
“edu/circa) and peritoneal macrophages (8).”
Self-citationAging disrupts circadian gene regulation and function in macrophages
Blacher, E., Tsai, C. A., Litichevskiy, L., Shipony, Z., Iweka, C. A., Schneider, K. M., Chuluun, B., Heller, H. C., Menon, V., Thaiss, C. A., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-01083-0 · Cited by 172
Koelsch, S., Boehlig, A., Hohenadel, M. G., Nitsche, I., Bauer, K., & Sack, U. (2016) · Scientific Reports · doi:10.1038/srep23008 · Cited by 177
BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders
Qiu, P., Jiang, J., Liu, Z., Cai, Y., Huang, T., Wang, Y., Liu, Q., Nie, Y., Liu, F., Cheng, J., et al. (2019) · National Science Review · doi:10.1093/nsr/nwz002 · Cited by 163
“The transcriptome results indicated overrepresentation of immunological and inflammatory responses upon BMAL1 ablation, consistent with the findings that several immune mediators are affected by circadian oscillations, thus weakening clock programs can lead to immune dysregulation [47], including abnormal regulation o…”
BackgroundA proteomics landscape of circadian clock in mouse liver
Wang, Y., Song, L., Liu, M., Ge, R., Zhou, Q., Liu, W., Li, R., Qie, J., Zhen, B., Wang, Y., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03898-2 · Cited by 147
Fernandez-Mendoza, J., Baker, J. H., Vgontzas, A. N., Gaines, J., Liao, D., & Bixler, E. O. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.12.026 · Cited by 155
The role of the circadian clock system in physiology
Pilorz, V., Helfrich‐Förster, C., & Oster, H. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-2103-y · Cited by 164
“Hence, disruption of circadian clocks and rhythms has detrimental effects on the immune function and pathogen responses [18, 88, 161].”
Lee, J., Kim, D. E., Griffin, P. Y., Sheehan, P. W., Kim, D., Musiek, E. S., & Yoon, S. (2019) · Aging Cell · doi:10.1111/acel.13078 · Cited by 158
“This revealed that, in peritoneal macrophages, the expression of several key clock components (Bmal1, Clock, Cry1, Cry2, Per1, Per2, Rev-erbα, and RORα) dynamically oscillated in a time-dependent manner (Figure 1c), in keeping with previous reports (Keller et al., 2009).”
ResultSimulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans
Cuesta, M., Boudreau, P., Dubeau‐Laramée, G., Cermakian, N., & Boivin, D. B. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502422 · Cited by 152
“The rhythmic functions, such as cytokine production, seem to be under the control of the immune clocks (19, 25, 28), whereas the number of circulating WBCs appears to be controlled by the central clock via humoral and neuronal signaling (18, 36, 37).”
BackgroundA cell-autonomous mammalian 12 hr clock coordinates metabolic and stress rhythms
Zhu, B., Zhang, Q., Pan, Y., Mace, E. M., York, B., Antoulas, A. C., Dacso, C. C., & O’Malley, B. W. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.004 · Cited by 146
“Due to the relatively poor resolution of the dataset (at 3 hr interval), we decided against the use of our eigenvalue/pencil approach but rather employed a more simplified but well-established CircWave software to only characterize proteins cycling with a dominant 12 hr period (Keller et al., 2009).”
MethodCircadian molecular clock in lung pathophysiology
Sundar, I. K., Yao, H., Sellix, M. T., & Rahman, I. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00152.2015 · Cited by 147
“The Toll-like receptor 4 (TLR4) pathway in peritoneal macrophages is regulated by the clock and may drive rhythmic variation in immune responses (86).”
Lananna, B. V., & Musiek, E. S. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104832 · Cited by 147
Circadian Clocks, Stress, and Immunity
Dumbell, R., Matveeva, O., & Oster, H. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00037 · Cited by 150
Circadian rhythm influences induction of trained immunity by BCG vaccination
de Bree, L. C. J., Mourits, V. P., Koeken, V. A. C. M., Moorlag, S. J. C. F. M., Janssen, R., Folkman, L., Barreca, D., Krausgruber, T., Fife, V. E. R., Novakovic, B., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133934 · Cited by 147
“Regulators of cytokine secretion and pathogen recognition receptors are examples of genes that have been shown to oscillate at a transcriptional level in a circadian manner in macrophages (26).”
BackgroundTarrant, J. M. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq134 · Cited by 139
“Fascinating is the recent work that establishes the presence of local and cell-autonomous circadian rhythms in lymphoid organs and peritoneal macrophages (Keller et al., 2009).”
BackgroundKitchen, G. B., Cunningham, P. S., Poolman, T. M., Iqbal, M., Maidstone, R. J., Baxter, M. D., Bagnall, J., Begley, N., Saer, B., Hussell, T., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1915932117 · Cited by 140
Circadian Rhythms of the Hypothalamus: From Function to Physiology
Drunen, R. V., & Eckel‐Mahan, K. L. (2021) · Clocks & Sleep · doi:10.3390/clockssleep3010012 · Cited by 146
Circadian Influence on Metabolism and Inflammation in Atherosclerosis
McAlpine, C. S., & Świrski, F. K. (2016) · Circulation Research · doi:10.1161/circresaha.116.308034 · Cited by 142
“For example, the Clock:Bmal1 heterodimer binds to toll-like receptor-9’s promoter sequence, thereby mediating its rhythmic expression in leukocytes.127 Furthermore, several components of macrophage toll-like receptor-4 signaling are circadian, including toll-like receptor-4 dimerization and the activity and expression…”
BackgroundInfluentialCircadian-Regulated Cell Death in Cardiovascular Diseases
Rabinovich-Nikitin, I., Lieberman, B., Martino, T. A., & Kirshenbaum, L. A. (2019) · Circulation · doi:10.1161/circulationaha.118.036550 · Cited by 137
The influence of biological rhythms on host–parasite interactions
Martinez, M. E., & Helm, B. (2015) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2015.03.012 · Cited by 139
Circadian disruption in the pathogenesis of metabolic syndrome
Maury, E., Hong, H. K., & Bass, J. (2014) · Diabetes & Metabolism · doi:10.1016/j.diabet.2013.12.005 · Cited by 132
“In ice, spleen, lymph nodes, and peritoneal macrophages conain intrinsic circadian clockworks that oscillate autonomously ven ex vivo [96].”
BackgroundInfluentialGrozinsky‐Glasberg, S., Franchi, G. M., Teng, M. J., Leontiou, C. A., de Oliveira, A. R., Ciaramella, P. D., Salahuddin, N., Korbonits, M., & Grossman, A. B. (2007) · Neuroendocrinology · doi:10.1159/000111501 · Cited by 130
Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease
Sutton, C. E., Finlay, C. M., Raverdeau, M., Early, J. O., DeCourcey, J., Zasłona, Z., O'Neill, L. A. J., Mills, K. H. G., & Curtis, A. M. (2017) · Nature Communications · doi:10.1038/s41467-017-02111-0 · Cited by 128
Time-of-Day-Dependent Trafficking and Function of Leukocyte Subsets
Pick, R., He, W., Chen, C.-S., & Scheiermann, C. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.03.010 · Cited by 136
Sleep Loss as a Factor to Induce Cellular and Molecular Inflammatory Variations
Hurtado‐Alvarado, G., Pavón, L., Castillo-García, S. A., Hernández, M. E., Domı́nguez-Salazar, E., Velázquez‐Moctezuma, J., & Gómez‐González, B. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/801341 · Cited by 130
“Macrophages and NK contain a cell-autonomous circadian clock [110, 111].”
BackgroundPeripheral Circadian Oscillators in Mammals
Brown, S. A., & Azzi, A. (2013) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25950-0_3 · Cited by 124
“Likewise, circadian clocks in macrophages (Keller et al. 2009) and T cells (Fortier et al.”
BackgroundGeiger, S. S., Fagundes, C. T., & Siegel, R. M. (2015) · Immunology · doi:10.1111/imm.12525 · Cited by 122
Wyse, C. A., O’Malley, G., Coogan, A. N., McConkey, S. J., & Smıth, D. J. (2021) · iScience · doi:10.1016/j.isci.2021.102255 · Cited by 122
Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome
Depner, C. M., Melanson, E. L., McHill, A. W., & Wright, K. P. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714813115 · Cited by 122
“Previous findings derived from mouse macrophages also suggest a role of the circadian clock in regulating ECM homeostasis (45), representing a potential link between the circadian clock and the immune system.”
BackgroundLifestyle Effects on Hematopoiesis and Atherosclerosis
Nahrendorf, M., & Świrski, F. K. (2015) · Circulation Research · doi:10.1161/circresaha.116.303550 · Cited by 124
Timing of circadian genes in mammalian tissues
Korenčič, A., Košir, R., Bordyugov, G., Lehmann, R., Rozman, D., & Herzel, H. (2014) · Scientific Reports · doi:10.1038/srep05782 · Cited by 119
The role of the circadian clock in rheumatoid arthritis
Gibbs, J. E., & Ray, D. W. (2013) · Arthritis Research & Therapy · doi:10.1186/ar4146 · Cited by 125
“Firstly, multiple immune cells possess the clockwork machinery and show daily variation in their function [6-8].”
The Cinderella syndrome: why do malaria-infected cells burst at midnight?
Mideo, N., Reece, S. E., Smith, A. L., & Metcalf, C. J. E. (2012) · Trends in Parasitology · doi:10.1016/j.pt.2012.10.006 · Cited by 116
PPAR-γ integrates obesity and adipocyte clock through epigenetic regulation of Bmal1
Wang, S., Lin, Y., Gao, L., Yang, Z., Lin, J., Ren, S., Li, F., Chen, J., Wang, Z., Dong, Z., et al. (2022) · Theranostics · doi:10.7150/thno.69054 · Cited by 119
“attributed to circadian inhibiting effects of TNF-, whose level varies with the times of the day [56,68].”
BackgroundMice exposed to dim light at night exaggerate inflammatory responses to lipopolysaccharide
Fonken, L. K., Weil, Z. M., & Nelson, R. J. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.08.011 · Cited by 118
Regulation of alternative splicing by the circadian clock and food related cues
McGlincy, N. J., Valomon, A., Chesham, J. E., Maywood, E. S., Hastings, M. H., & Ule, J. (2012) · Genome biology · doi:10.1186/gb-2012-13-6-r54 · Cited by 115
“Furthermore, the susceptibility of mice to Escherichia coli endotoxin-induced mortality shows a marked circadian rhythm [46]; this is reflected by circadian variation in the amount of pro-inflammatory cytokines (TNF-a and IL-6) produced by splenic macrophages in response to challenge with bacterial endotoxin (lipopoly…”
Background
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)
- 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
- 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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