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 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.
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.
Integrity signals
Registry
Cites
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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).”
From About Sleep's Role in Memory (2013) · cites this paper as [627]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measured
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
LPS/TLR4 signal transduction pathway
Lu, Y.-C., Yeh, W.-C., & Ohashi, P. S. (2008) · Cytokine · doi:10.1016/j.cyto.2008.01.006 · Cited by 3,301
Yoo, S.-H., Yamazaki, S., Lowrey, P. L., Shimomura, K., Ko, C. H., Buhr, E. D., Siepka, S. M., Hong, H.-K., Oh, W. J., Yoo, O. J., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308709101 · Cited by 2,329
Resetting central and peripheral circadian oscillators in transgenic rats
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
Transplanted Suprachiasmatic Nucleus Determines Circadian Period
Ralph, M. R., Foster, R. G., Davis, F. C., & Menaker, M. (1990) · Science · doi:10.1126/science.2305266 · Cited by 1,853
The genetics of mammalian circadian order and disorder: implications for physiology and disease
Takahashi, J. S., Hong, H.-K., Ko, C. H., & McDearmon, E. L. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2430 · Cited by 1,611
Haematopoietic stem cell release is regulated by circadian oscillations
Méndez‐Ferrer, S., Lucas, D., Battista, M., & Frenette, P. S. (2008) · Nature · doi:10.1038/nature06685 · Cited by 1,310
Physiological significance of a peripheral tissue circadian clock
Lamia, K. A., Storch, K.-F., & Weitz, C. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806717105 · Cited by 1,048
Anti-inflammatory actions of steroids: molecular mechanisms
Barnes, P. J., Adcock, I. M., Spedding, M., & Vanhoutte, P. M. (1993) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(93)90184-l · Cited by 725
How (and why) the immune system makes us sleep
Imeri, L., & Opp, M. R. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2576 · Cited by 710
Cited by
Sorted by citations
Items 601–700 of 841
Singh, J., Baxi, S., & Ashdown, M. L. (2025) · Chronobiology International · doi:10.1080/07420528.2025.2538581 · Cited by 4
“The following studies have smartly found that the secretion profile of multiple proinflammatory cytokines displays a circadian rhythm (Cash et al. 2021; Gibbs et al. 2012, 2014; Haspel et al. 2020Nakao 2014, Keller et al. 2009; Scheiermann et al. 2018).”
InfluentialDCPR: a deep learning framework for circadian phase reconstruction
Han, X., Cen, X., Li, Z., Zhou, X., & Ji, Z. (2025) · BMC Bioinformatics · doi:10.1186/s12859-025-06363-2 · Cited by 5
“To identify seed genes for DCPR modeling, we analyzed two Mus musculus (mouse) datasets (GSE54651 [29], GSE25585 [30]) and one Papio anubis (olive baboon) dataset (GSE98965 [31]), using the non-parametric algorithm JTK_CYCLE at CircaKB online platform [32], and identified 110, 592, and 711…”
Zhang, T., Zhang, G., Liu, T., Gu, T., Yu, F., Xu, P., Mi, W., Zhao, X., Guo, Q., Zheng, H., et al. (2026) · Med Research · doi:10.1002/mdr2.70052 · Cited by 4
When Clocks Go Rogue: Circadian Rhythms and the Rise of Cancer
Robinson, A. S., Bennett, S. E., & Sato, S. (2026) · Journal of Biological Rhythms · doi:10.1177/07487304251391270 · Cited by 4
“Their intrinsic clock controls 8% of their transcriptome and regulates their inflammatory innate immune functions, with the surrounding environment significantly impacting their response and polarization (Keller et al., 2009).”
Chen, Y., Huang, P., Chai, C., Yu, S., Hsieh, Y., Chang, H.-C., Kuo, C.-W., Lee, Y.-C., & Yu, H. (2022) · The Analyst · doi:10.1039/d2an01546c · Cited by 4
Balit, N., Cermakian, N., & Khadra, A. (2024) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2024.111852 · Cited by 4
Notch1 siRNA and AMD3100 Ameliorate Metabolic Dysfunction-Associated Steatotic Liver Disease
Zhu, C., Cheng, Y., Yang, L., Lyu, Y., Li, J., Zhao, P., Zhu, Y. J., Xin, X., & Yin, L. (2025) · Biomedicines · doi:10.3390/biomedicines13020486 · Cited by 5
“For instance, macrophages have a circadian clock that regulates the rhythmic secretion of TNF and IL-6 [58], which leads to macrophages exhibiting a marked circadian rhythmic pattern in the secretion of TNF-α and IL-6, with a peak-to-trough ratio of approximately 3 [59].”
Circadian clock gene disruption in white blood cells of patients with celiac disease
Weintraub, Y., Cohen, S., Yerushalmy‐Feler, A., Chapnik, N., Tsameret, S., Anafy, A., Damari, E., Ben‐Tov, A., Shamir, R., & Froy, O. (2023) · Biochimie · doi:10.1016/j.biochi.2023.07.020 · Cited by 4
Yang, Y., He, X., Zhao, Z., & Yi, J. (2024) · Cureus · doi:10.7759/cureus.66621 · Cited by 4
“Meanwhile, human macrophage behavior is influenced by individual medical history, microbiome composition, and circadian rhythms, making accurate prediction of their responses challenging [130,131].”
BackgroundKulhavá, L., Houdek, P., Nováková, M., Hričko, J., Paucova, M., Kuda, O., Sládek, M., Fiehn, O., Sumová, A., & Čajka, T. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05783-w · Cited by 4
Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle
Rajavel, A., Schmitt, A. O., & Gültaş, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020562 · Cited by 4
“Circadian clock related pathways in Table 4 can be categorised as the most prominent pathways in the spleen tissue due to the circadian control of splenic macrophages and B-cell development [107,145] (see Figure 4).”
BackgroundFeeding Pattern, Circadian Rhythm, and Immune Function: What do we know about?
Estanislau, T. B., Kruger, K., Neto, J. C. R., Padilha, C. S., Gonçalves, D. C., Minuzzi, L. G., & Lira, F. S. (2022) · Current Pharmaceutical Design · doi:10.2174/1381612828666220729091451 · Cited by 5
The Assessment of Circadian Rhythms Within the Immune System
Nobis, C. C., Cuesta, M., Daudelin, J., Laramée, G. D., Boivin, D. B., Labrecque, N., & Cermakian, N. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0381-9_3 · Cited by 4
Rudyk, M. P., Fedorchuk, O., Susak, Y. M., Nowicky, Y., & Skivka, L. M. (2016) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2016.02.004 · Cited by 4
Carbone, A., Santis, E. D., Cela, O., Giambra, V., Miele, L., Marrone, G., Grieco, A., Buschbeck, M., Capitanio, N., Mazza, T., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9081057 · Cited by 4
“This pattern could be rel ted to the macroH2A1 histone-linked epige etic landscape and the bi logical clock’s ability to ontrol the expression of metalloproteinases, whic play a crucial role in inflamma ory process , extracellular ma rix homeostasis, wound healing, and cancer cell migration [75,76] (Figure 3).”
BackgroundEditorial: Circadian Control of Immunity
Ikuta, K., & Scheiermann, C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.618843 · Cited by 4
“The cell type that so far has been investigated in most detail is the macrophage (5, 6).”
BackgroundOrganismal landscape of clock cells and circadian gene expression in DrosophilaPreprint
Patop, I. L., Anduaga, A. M., Bussi, I. L., Ceriani, M. F., & Kadener, S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.23.542009 · Cited by 4
Effects of dim light at night in C57BL/6 J mice on recovery after spinal cord injury
Aldrich, J. C., Scheinfeld, A. R., Lee, S. E., Dusenbery, K. J., Mahach, K. M., de Veire, B. C. V., Fonken, L. K., & Gaudet, A. D. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114725 · Cited by 3
Matak, A. M., Mu, Y., Mohati, S. M., Makdissi, S., & Cara, F. D. (2025) · Genome · doi:10.1139/gen-2025-0003 · Cited by 3
Circadian metabolism in myeloid cells
Xu, Y., Wang, C., & Ho, P. (2025) · Life Metabolism · doi:10.1093/lifemeta/loaf018 · Cited by 3
Impact of toll-like receptors on food allergy: mechanisms involved and scientific evidence
Álvarez-Azcarreta, S., Mountasar-Didouch, W., Macho‐González, A., & Sánchez-Muniz, F. J. (2025) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-025-01111-9 · Cited by 3
“Beyond TLR expression, cytokine production by macrophages and CD4 + T cells are also under circadian control [9] as are the suppressor function of FoxP3 + Treg cells, leukocyte trafficking, and antibody production [27].”
Skin and immune cells crosstalk via circadian regulations
Orihara, K. (2021) · Exploration of Immunology · doi:10.37349/ei.2021.00019 · Cited by 3
“Moreover, these circadian clocks can be operated autonomously without signals from the central clock [29].”
BackgroundCircadian Rhythms in Ischemic Stroke: From Molecular Pathways to Chronotherapeutic Strategies
Deb, S., Mondal, R., Sarkar, V., Shome, G., Mete, R., Sarkar, S., Das, S., Roy, J., & Benito‐León, J. (2025) · European Neurology · doi:10.1159/000548456 · Cited by 3
“Neutro-phils, the most abundant leukocytes in human blood, play a crucial role in the inflammatory response following injury [45].”
Impact of operation timing on post‐operative infections following colorectal cancer surgery
Li, C., An, X., Zhao, B., Wu, S., Xie, G., & Fang, X. (2016) · ANZ Journal of Surgery · doi:10.1111/ans.13471 · Cited by 3
“Recruitment of immune cells into tissues is known to be under circadian control,(5,6) and several pro-inflammatory cytokines have been shown to exhibit robust oscillations.(7,8) An increasing body of evidence indicates that susceptibility to endotoxic shock is dependent on the circadian rhythm.”
BackgroundRegulation of Immunity by the Circadian Clock
de Juan, A., Druzd, D., Ince, L. M., & Scheiermann, C. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3450-8_9 · Cited by 3
Polónia, J. J. (2017) · Revista Portuguesa de Cardiologia · doi:10.1016/j.repc.2016.12.003 · Cited by 3
A selective window after the food-intake period favors tolerance induction in mesenteric lymph nodes
Barrios, B. E., Macció-Maretto, L., Nazar, F. N., & Correa, S. G. (2018) · Mucosal Immunology · doi:10.1038/s41385-018-0095-3 · Cited by 3
Coulibaly, F. S., Ezoulin, M. J. M., Dim, D. C., Molteni, A., & Youan, B.-B. C. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00872 · Cited by 3
Steinach, M., & Gunga, H. (2019) · Springer eBooks · doi:10.1007/978-3-030-16996-1_9 · Cited by 4
Buel, S. M., Debopadhaya, S., Santos, H. D. L., Edwards, K. M., David, A. M., Dao, U. H., Bennett, K. P., & Hurley, J. (2022) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkac176 · Cited by 4
“CT was calculated based on peak and trough Per2 expression of ex vivo peritoneal macrophages as reported in Keller et al. (2009).”
Biological Clocks and Immune Function
Walker, W. H., Meléndez‐Fernández, O. H., Becker‐Krail, D. D., & Nelson, R. J. (2023) · Masterclass in neuroendocrinology · doi:10.1007/978-3-031-21358-8_11 · Cited by 3
Nam, H., Kim, B., Lee, Y. H., Choe, H. K., & Yu, S. (2023) · Experimental Neurobiology · doi:10.5607/en23012 · Cited by 3
“Other immune cells, astrocytes and BMDM, also have an intrinsic molecular clock and are associated with circadian regulation [16, 29].”
BackgroundCabral, P. C., Stegeman, S. K., Olivier, M., & Cermakian, N. (2024) · Parasite Immunology · doi:10.1111/pim.13053 · Cited by 3
“Nevertheless, transcriptional activation of pro-inflammatory cytokines by clock proteins is well known, including rhythms in TNFα [24].”
BackgroundInfluentialCircadian Rhythms, Immune Regulation, and the Risk for Sepsis
Sengupta, S., Smith, D. F., & Koritala, B. S. C. (2024) · Clinics in Perinatology · doi:10.1016/j.clp.2024.10.012 · Cited by 3
Circadian immune system in solid organ transplantation: a review article
Yim, W. Y., Li, C., Tong, F., Hou, J., Chen, Y., Liu, Z., Wang, Z., Geng, B., Wang, Y., & Dong, N. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1556057 · Cited by 3
Mechanistic Modeling of Inflammation
Scheff, J. D., Kamisoglu, K., & Androulakis, I. P. (2016) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-319-44534-2_15 · Cited by 3
Endogenous Seasonal Variation in the Encapsulation Response of the Noble Crayfish (Astacus astacus)
Gruber, C., Vainikka, A., Hirvonen, H., Rantala, M. J., & Kortet, R. (2014) · Annales Zoologici Fennici · doi:10.5735/086.051.0504 · Cited by 3
Role of Astrocytes in the Immune-Circadian Signaling
Duhart, J. M., Marpegán, L., Leone, M. J., & Golombek, D. A. (2013) · Advances in Neuroimmune Biology · doi:10.3233/nib-130058 · Cited by 3
Burn trauma disrupts circadian rhythms in rat liver.
Rao, R., Yang, Q., Orman, M. A., Francois Berthiaume, B., Ierapetritou, M., & Androulakis, I. P. (2016) · Europe PMC (PubMed Central) · Cited by 3
The role for the microbiome in the regulation of the circadian clock and metabolism
Anderson, S. T., & Paschos, G. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816843-1.00015-1 · Cited by 3
An Introduction to Circadian Endocrine Physiology: Implications for Exercise and Sports Performance
Okusaga, O. O., & Postolache, T. T. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-314-5_20 · Cited by 3
Steinach, M., & Gunga, H. (2011) · Springer eBooks · doi:10.1007/978-3-642-22272-6_7 · Cited by 3
Bushell, D., Tan, J. K. H., Smith, J. K., & Moro, C. (2023) · Laboratory Medicine · doi:10.1093/labmed/lmad062 · Cited by 2
Chikungunya Virus, Metabolism, and Circadian Rhythmicity Interplay in Phagocytic Cells
Alvarez-García, L., Sánchez‐García, F. J., Vázquez-Pichardo, M., & Moreno‐Altamirano, M. M. B. (2023) · Metabolites · doi:10.3390/metabo13111143 · Cited by 3
“Subjects injected with low doses of LPS at midday show higher levels of IL-10, whereas exposure to LPS after midnight increases the levels of tumor necrosis factor (TNF) and IL-6 [8,77].”
BackgroundJakobs, M., Tebbe, B., Friedel, A. L., Schönberger, T., Engler, H., Wilde, B., Fandrey, J., Hörbelt, T., & Schedlowski, M. (2024) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00247.2024 · Cited by 2
Dong, C., Li, B., Liu, C., Cui, J., Li, Y., Liang, L., Song, Y., & Li, X. (2025) · Environment & Health · doi:10.1021/envhealth.5c00031 · Cited by 2
Mazur, M., Pijanowski, Ł., Adamek, M., Matras, M., Rakus, K. Ł., & Chadzińska, M. (2025) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2025.110525 · Cited by 2
The circadian clock regulates innate immunity and cardiovascular diseases
Qiu, D., Li, L., Yu, X., Xiao, Z., Chen, K., Wang, Z., & Wang, S. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178050 · Cited by 2
BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity
Philippe, M., Fruchet, B., Cagninacci, L., Beaudoin, L., Gadault, A., Aznar, B., Venteclef, N., Challet, É., Lehuen, A., Rogner, U. C., et al. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156396 · Cited by 2
Liu, X., Fang, J., Cheng, D., Luan, W., Lv, Y., Hu, W., Pan, L., & Zhang, Y. (2025) · Advanced Science · doi:10.1002/advs.202514388 · Cited by 3
By dawn or dusk—how circadian timing rewrites bacterial infection outcomes
Mo, D., Palmer, C. S., & Kimmey, J. M. (2025) · FEBS Letters · doi:10.1002/1873-3468.70212 · Cited by 2
Crosstalk between Circadian Rhythm and Neuroinflammation
Mei, G., Pan, H., Zheng, J., Chen, K., Zheng, W., Xu, H., Liu, Z., Lin, Lin, Z., & Zhang, M. (2026) · Neuroendocrinology · doi:10.1159/000551312 · Cited by 4
Nakanishi, H. (2014) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12161 · Cited by 3
“including genes involved in the Toll-like receptor 4 pathway.(26) These observations of peritoneal macrophages”
BackgroundCharacteristics of Sleep in Critically Ill Patients: Part II: Circadian Rhythm Disruption
Mélone, M.-A., & Gehlbach, B. K. (2022) · Springer eBooks · doi:10.1007/978-3-031-06447-0_2 · Cited by 2
CIRCADIAN RHYTHMS FOR CYTOKINES
Радаева, О. А., Kostina, Y. A., Solodovnikova, G. A., Anashkina, E. V., Iskandyarova, M. S., Негоднова, Е. В., & Mashnina, S. V. (2023) · Современные проблемы науки и образования · doi:10.17513/spno.32778 · Cited by 3
Influence of shift work on periodontitis according to the occupation group
Jung, S., Lim, H., Jeong, Y., Lee, S., Park, J. S., & Song, I. (2023) · Scientific Reports · doi:10.1038/s41598-023-45222-z · Cited by 2
Wang, S., Chen, Y., Zhou, H., Ning, Z., Hu, T., Ye, C., & Mu, W. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.128310 · Cited by 2
A circadian clock regulates the blood-brain barrier across phylogeny
Avila, A., & Zhang, S. (2024) · Vitamins and hormones · doi:10.1016/bs.vh.2024.04.004 · Cited by 2
Circadian Regulation of Sleep: From Genes to Circuits
Hameed, N. A., & Barber, A. F. (2024) · Springer eBooks · doi:10.1007/978-3-031-62723-1_14 · Cited by 3
Nanobiosystems-based chronotherapeutics in treatment of asthma
Patel, M. C., Indurkhya, A., Prajapati, A., Parashar, A. K., Saraogi, G. K., & Mishra, V. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-90254-0.00005-2 · Cited by 2
Chen, Q., Wang, W., Fang, W., Qin, L., Wang, J., Huang, X., Pan, S., & Zheng, R. (2025) · genesis · doi:10.1002/dvg.70014 · Cited by 2
“In Maren Keller study, they identified circadian clock genes were rhythmically expressed in macrophages (Keller et al. 2009) Consistent with the results of Maren Keller, we also demonstrated the circadian rhythms of clock genes in macrophages in control Bmal1 flox/flox mice.”
Qin, C., Memon, N. H., Gong, Q., Shi, Q., & Yang, Q. (2021) · Chronobiology International · doi:10.1080/07420528.2021.1927070 · Cited by 2
“Mammals exhibit daily oscillations in multiple aspects of immune function, such as lymphocyte proliferation, antibacterial factors, cytokines, and hematopoietic cells as well as neutrophils and macrophages (Bollinger et al. 2011; Keller et al. 2009).”
BackgroundCircadian Rhythm Affects the Dynamics of S-IgA Mucosal Secretion
Kobayashi, R., Taguchi, C., Yonenaga, S., Arikawa, K., Uchiyama, T., Kôno, T., Takeuchi, T., Nasu, I., Hirano, H., & Ochiai, T. (2015) · International Journal of Oral-Medical Sciences · doi:10.5466/ijoms.14.1 · Cited by 2
“We thus hypothesized that Ab-producing B cells are strictly regulated by clock genes(3, 5, 9, 15).”
BackgroundYe, H., Yang, K., Tan, X., Zhao, D., Lü, X., & Wang, Q. (2015) · PubMed Central · doi:10.7518/hxkq.2015.05.016 · Cited by 2
Alibhai, F. J., Tsimakouridze, E. V., Reitz, C. J., Pyle, W. G., & Martino, T. A. (2016) · Springer eBooks · doi:10.1007/978-1-4939-3450-8_8 · Cited by 1
[Regulation of ILC3/Th17-Mediated Intestinal Immune Response by Circadian Rhythm].
Chang, J., & Qiu, J. (2022) · 四川大学学报：医学版 · doi:10.12182/20220160502 · Cited by 2
A Unified Computational Model for the Human Response to Lipopolysaccharide-Induced Inflammation
Windoloski, K. A., Bangsgaard, E. O., Dobréva, A., Ottesen, J. T., & Olufsen, M. S. (2022) · Mathematics online first collections · doi:10.1007/16618_2022_39 · Cited by 2
Cantos-Barreda, A., Escribano, D., Egui, A., López, M. C., Cerón, J. M. C., Bernal, L. J., & Martı́nez-Subiela, S. (2019) · Comparative Immunology Microbiology and Infectious Diseases · doi:10.1016/j.cimid.2019.101389 · Cited by 2
Circadian Rhythms in Immune Function
Adams, K. L., Castañón‐Cervantes, O., & Davidson, A. J. (2015) · Wiley eBooks · doi:10.1002/9781118467831.ch14 · Cited by 2
Harding, C. L. (2020) · ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · doi:10.18297/etd/3506 · Cited by 2
Oshinowo, T., Maples, R. W., Acevedo, M. A. W., McCune, B. T., Dalton, H., Johnson, I., Simpkins, D., Basu, U., Dende, C., Tarakanova, V. L., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.15.725500 · Cited by 2
Alvarenga, B. O. E., Biavatti, A. M., & Ferreira, A. J. P. (2021) · Veterinária notícias/Veterinária Notícias · doi:10.14393/vtn-v27n2-2021-57951 · Cited by 1
Circadian Rhythms and the Treatment of Rheumatoid Arthritis
Lee, Y. (2021) · Archives of Rheumatology & Arthritis Research · doi:10.33552/arar.2021.01.000515 · Cited by 1
“factors, which, in turn modulate the circadian phases of body clock systems [17,18].”
BackgroundSearching for Order in Body Clocks: Circadian Rhythms and Redox Balance
del Olmo, M. (2021) · Logos Verlag Berlin eBooks · doi:10.30819/5406 · Cited by 1
Hsieh, Y., Huang, S.-M., Yu, S., Chao, T.-N., Chiang, C.-W., Kan, Y.-Y., Chang, Y., Kuo, L., & Yu, H. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121259 · Cited by 1
“Excessive exposure to light at night can disrupt circadian rhythm and lead to inflammatory immune responses (Keller et al., 2009).”
Dai, P., & Liu, J. (2025) · Health and Metabolism · doi:10.53941/hm.2025.100017 · Cited by 1
“The activity of 5-LOX ends to peak during early morning hours, coinciding with increased inflammatory responses, as LTs levels rise in response to circadian signals [39].”
Jiao, H., Jermei, J., Liang, X., van der Zande, H. J. P., Vrieling, F., Rumanova, V. S., Dorscheidt, M., Corrêa‐da‐Silva, F., Wang, A., Foppen, E., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116380 · Cited by 1
Copper regulates the expression of immune genes in microglial cells in vitro
Craciun, L., Muroy, S. E., & Saijo, K. (2025) · Immunobiology · doi:10.1016/j.imbio.2025.153145 · Cited by 3
“…et al., 1998; Buscher et al., 2017; Naigles et al., 2023), technical variability (Kemfack et al., 2022; Wilfinger et al., 2023), circadian rhythms (Keller et al., 2009; Wang et al., 2016; Zeng et al., 2024), cell cycle stages (D’Angelo et al., 2017), and microenvironmental factors such as cell…”
Haddad, M., Trzebanski, S., Ramos, R. B., Moreno, L. O., Rahtes, A., Khatib-Massalha, E., Chakrabarti, P., Petrovich‐Kopitman, E., Wigoda, N., Biram, A., et al. (2025) · European Journal of Immunology · doi:10.1002/eji.70077 · Cited by 1
The Keto–Inflammatory Network: From Systems Biology to Biological Code
Ametaj, B. N. (2026) · Dairy · doi:10.3390/dairy7010019 · Cited by 2
Lin, Y.-N., Peng, W., Huang, Y.-C., Lai, C., Hsu, J., Wang, J.-Y., Kao, Y.-C., & Wu, L. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08000-9 · Cited by 1
“Prior studies have demonstrated that SCFAs can modulate host gene expression through histone deacetylase inhibition and signaling via FFAR2/3 and HCAR2 , and that indole derivatives may engage AHR-dependent pathways [28, 31].”
Mizutani, A., Parra-Pérez, C., Shindo, A., Lizasoaín, I., Moro, M. Á., & Arai, K. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261437523 · Cited by 3
A temporal dialogue between the circadian clock and chronic inflammatory diseases
Chen, S., & Ray, D. W. (2026) · Disease Models & Mechanisms · doi:10.1242/dmm.052749 · Cited by 2
“…reveal gated immune responses: in vitro in spleen cells, lipopolysaccharide (LPS)-induces peaks of IL-6 and TNF-α at the late sleep phase (Keller et al., 2009); in vivo , LPS-induced IL-6, IL-12, CXCL1, CCL2 and CCL5 levels in serum are significantly higher when LPS was given at the…”
Circadian rhythms, NRF2 signalling and redox homeostasis: A holy grail for a healthy life course?
Sutton, E., & Pekovic‐Vaughan, V. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.05.318 · Cited by 2
El-Nablaway, M., & Koushaji, G. (2026) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2026.102644 · Cited by 1
Asif, S., Mitchell, J. W., & Gillette, M. U. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27135729 · Cited by 1
“Around eight percent of the macrophage transcriptome is circadian-controlled [133].”
Liu, J.-G., Chen, J., Luo, Z., Chen, Y., Yuan, S., & Li, J. B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1891187 · Cited by 1
“At the molecular level, circadian variation in clock gene expression has been documented across multiple immune cell types, including monocytes, macrophages, neutrophils, dendritic cells and lymphocytes (26).”
Statistical considerations when analyzing biomarker data
Beam, C. A. (2015) · Clinical Immunology · doi:10.1016/j.clim.2015.05.019 · Cited by 1
Innate Immune Reactions in an Invertebrate, Pacifastacus leniusculus
Watthanasurorot, A. (2013) · Cited by 1
Modeling Circadian Rhythms in Inflammation
Scheff, J. D., Androulakis, I. P., Calvano, S. E., & Lowry, S. F. (2010) · IEEE International Conference on Bioinformatics and Bioengineering (BIBE) · doi:10.1109/bibe.2010.39 · Cited by 1
“Several studies have shown that most cytokines undergo diurnal variations in plasma levels, typically peaking in the night [20-24], but the specific mechanism that drives these changes is not clear [ 25 ].”
BackgroundChronotherapy: a noteworthy focal point in the treatment of cancer?
Subramanian, P., Jayapalan, J. J., & Hashim, O. H. (2014) · Biological Rhythm Research · doi:10.1080/09291016.2014.905346 · Cited by 1
“Other immune cells contain molecular clock machinery includes macrophages, B- and T-cells (Keller et al. 2009).”
BackgroundCircadian Clocks and Immune Functions
Nobis, C. C., Kießling, S., Labrecque, N., & Cermakian, N. (2017) · Springer eBooks · doi:10.1007/978-81-322-3688-7_22 · Cited by 1
Wang, Z., & Kamioka, H. (2017) · Journal of Oral Biosciences · doi:10.1016/j.job.2017.11.001 · Cited by 1
Arias, J. L., Mayordomo, A. C., Silva, J. C., Ragusa, J. A. V., Rabinovich, G. A., Anzulovich, A. C., & Genaro, M. S. D. (2018) · NeuroImmunoModulation · doi:10.1159/000493143 · Cited by 1
Overview and Understanding of Human Circadian Immunology
Padem, N., & Fishbein, A. B. (2019) · Springer eBooks · doi:10.1007/978-3-030-14738-9_4 · Cited by 1
Polónia, J. J. (2017) · Revista Portuguesa de Cardiologia (English Edition) · doi:10.1016/j.repce.2017.02.005 · Cited by 1
Microbiome Composition and Circadian Rhythm Disruption Alters Epithelial Barrier Integrity
Pinker, E. Y., & Tuganbaev, T. (2021) · Columbia Undergraduate Science Journal · doi:10.52214/cusj.v15i1.7408 · Cited by 1
“The circadian clock is the top of a hierarchical internal clock system that is responsible for the circadian biological processes ranging from dictating the rhythmic gene expression in organs to behavior, metabolism and immunity [10][11].”
BackgroundLouden, N. P. (2010) · Digital Commons - USU (Utah State University) · doi:10.26076/9f24-52bc · Cited by 1
Sleep and vaccine administration time as factors influencing vaccine immunogenicity
Kim, E. S., & Oh, C. E. (2022) · Kosin Medical Journal · doi:10.7180/kmj.22.014 · Cited by 1
“For example, when endotoxins stimulate macrophages, the amount of tumor necrosis factor alpha (TNF-α) secreted by macrophages shows a circadian pattern according to the injection time of the endotoxin [12].”
BackgroundCircadian rhythmicity and vaccination
Moreno‐Altamirano, M. M. B., Oliva, J., & Sánchez‐García, F. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85941-7.00007-3 · Cited by 1
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
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
