Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses — ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation —are mediated in a time of day–dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, “Sleep Insufficiency, Circadian Misalignment, and the Immune Response,” to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation.
Jeffrey A. Haspel, Ron Anafi, Marishka K. Brown, Nicolas Cermakian, Christopher Depner, Paula Desplats, Andrew E. Gelman, Monika Haack, Sanja Jelic, Brian S. Kim, Aaron D. Laposky, Yvonne C. Lee, Emmanuel Mongodin, Aric A. Prather, Brian J. Prendergast, Colin Reardon, Albert C. Shaw, Shaon Sengupta, Éva Szentirmai, Mahesh Thakkar, Wendy E. Walker, Laura A. Solt
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Circadian Rhythm Disruption Exacerbates Autoimmune Uveitis: The Essential Role of PER1 in Treg Cell Metabolic Support for Stability and Function
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Advanced Science | 2025 |
Determinants of Multimorbidity in a Low-Resource Setting: A Population-Based Cross-Sectional Study in Bangladesh
Noor ST, Kawsar LA, Bhuia MR |
Global Health, Epidemiology and Genomics | 2025 |
Time of the Day of Traumatic Brain Injury has Minimal Effects on Behavioral and Histological Outcomes in Mice of Both Sexes
Davis CK, Jeong S, Subramanian S, Choi J, Ostrom CM, Park S, Vemuganti R |
Neuromolecular medicine | 2025 |
The clinical impact of chronopharmacology on current medicine.
Kaşkal M, Sevim M, Ülker G, Keleş C, Bebitoğlu BT |
Naunyn-Schmiedeberg's archives of pharmacology | 2025 |
Chronotherapy and intervertebral disc degeneration: understanding the role of circadian rhythm in degenerative processes
Zhang C, Zhang R, Zhao G, Wu Z, Song W, Ran R, Zhou K, Zhang H |
Frontiers in Cell and Developmental Biology | 2025 |
M54 selectively stabilizes the circadian clock component of CRY1 and enhances the period of circadian rhythm at cellular level
Gül ZM, Aydoğan S, Sürme S, Harputluoğlu Efendi SN, Özcan O, Uyanık E, Baris I, Gül S, Kavakli IH |
The Journal of Biological Chemistry | 2025 |
Effect of a saffron extract on sleep quality in adults with moderate insomnia: A decentralized, randomized, double-blind, placebo-controlled trial
Schuster J, Mundhenke C, Nordsieck H, Pouchieu C, Pourtau L, Hahn A |
Sleep Medicine: X | 2025 |
The intricate link between circadian rhythms and aging: can resetting our circadian clock hold the key to longevity?
Hassan NU, Smith WK, Nawaz HA, Wang H |
Biogerontology | 2025 |
Bidirectional Crosstalk Between Sleep and Pulmonary Arterial Hypertension
Imani S, Halouani A, Dahlka J, Burgess N, Antar S, Zhao YY, Chan SY, West JD, Weston M, Sassi Y |
bioRxiv | 2025 |
A Narrative Review on How Timing Matters: Circadian and Sleep Influences on Influenza Vaccine Induced Immunity
Livieratos A, Zeitzer JM, Tsiodras S |
Vaccines | 2025 |
From Lockdowns to Long COVID—Unraveling the Link Between Sleep, Chronotype, and Long COVID Symptoms
Tsaava M, Basishvili T, Sakhelashvili I, Eliozishvili M, Oniani N, Lortkipanidze N, Tarielashvili M, Khoshtaria L, Darchia N |
Brain Sciences | 2025 |
Circadian rhythms of macrophages are altered by the acidic pH of the tumor microenvironment
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2024 | |
Move the night way: how can physical activity facilitate adaptation to shift work?
Easton DF, Gupta CC, Vincent GE, Ferguson SA |
Communications biology | 2024 |
The role of circadian clock in regulating cell functions: implications for diseases.
Lin Y, He L, Cai Y, Wang X, Wang S, Li F |
2024 | |
Identification of circadian rhythm-related gene classification patterns and immune infiltration analysis in heart failure based on machine learning
Wang X, Rao J, Zhang L, Liu X, Zhang Y |
Heliyon | 2024 |
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Journal for ImmunoTherapy of Cancer | 2024 |
Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders
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International journal of molecular sciences | 2024 |
Sleep duration time and human papillomavirus infection risk: The U-shaped relationship revealed by NHANES data
Hu H, Wu Y, Zhao M, Liu J, Xie P |
PloS one | 2024 |
RAR-related orphan receptor alpha and the staggerer mice: a fine molecular story.
Rani A |
Frontiers in Endocrinology | 2024 |
One Health: Circadian Medicine Benefits Both Non-human Animals and Humans Alike.
Farag HI, Murphy BA, Templeman JR, Hanlon C, Joshua J, Koch TG, Niel L, Shoveller AK, Bedecarrats GY, Ellison A, Wilcockson D, Martino TA |
Journal of Biological Rhythms | 2024 |
Influence of the spaceflight environment on macrophage lineages
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npj Microgravity | 2024 |
Exploring the Role of Circadian Rhythms in Sleep and Recovery: A Review Article
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Cureus | 2024 |
Researchers need to better address time-of-day as a critical biological variable
Nelson RJ, DeVries AC, Prendergast BJ |
Proceedings of the National Academy of Sciences | 2024 |
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Sagtaganov Z, Bekaryssova D |
Rheumatology International | 2024 |
The Triad of Sleep, Immunity, and Cancer: A Mediating Perspective
Lanza G, Mogavero MP, Salemi M, Ferri R |
Cells | 2024 |
Sleep patterns, physical activity, genetic susceptibility, and incident rheumatoid arthritis: a prospective cohort study
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BMC Medicine | 2024 |
Deciphering a Beetle Clock: Individual and Sex-Dependent Variation in Daily Activity Patterns
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Journal of Biological Rhythms | 2024 |
Effect of aberrant fructose metabolism following SARS-CoV-2 infection on colorectal cancer patients' poor prognosis.
Jiang J, Meng X, Wang Y, Zhuang Z, Du T, Yan J |
PLoS computational biology | 2024 |
Circadian rhythms of macrophages are altered by the acidic tumor microenvironment.
Knudsen-Clark AM, Mwangi D, Cazarin J, Morris K, Baker C, Hablitz LM, McCall MN, Kim M, Altman BJ |
EMBO reports | 2024 |
The influence of light on Interleukin-10: A preliminary study
Mekschrat L, Göring M, Schmalbach B, Rohleder N, Petrowski K |
Brain, Behavior, & Immunity - Health | 2024 |
Bidirectional Interaction of Sepsis and Sleep Disorders: The Underlying Mechanisms and Clinical Implications.
Guo DZ, Chen Y, Meng Y, Bian JJ, Wang Y, Wang JF |
Nature and science of sleep | 2024 |
A randomized clinical trial of the impact of melatonin on influenza vaccine: Outcomes from the melatonin and vaccine response immunity and chronobiology study (MAVRICS)
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Human Vaccines & Immunotherapeutics | 2024 |
Time of day dependent reduction in stroke infarct volume by the Reverb agonist SR9009 in mice
Kamat PK, Khan MB, Siddiqui S, Hattaway TG, Anas A, Rudic. RD, Baban B, Dhandapani KM, Hess DC |
Experimental neurology | 2024 |
Neuro-immune cell interactions in the regulation of intestinal immune homeostasis
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Current opinion in gastroenterology | 2024 |
ClinCirc identifies alterations of the circadian peripheral oscillator in critical care patients
Peter Cunningham, Gareth Kitchen, Callum Jackson, Stavros Pappachristos, Tom Springthorpe, David Vandellen, Julie Gibbs, Timothy Felton, Anthony Wilson, Jonathan Bannard-Smith, Martin Rutter, Thomas House, Paul Dark, Titus Augustine, Ozgur Akman, Andrew Hazel, John Blaikley |
Journal of Clinical Investigation | 2023 |
BIOLOGICAL RHYTHMS IN COVID-19 VACCINE EFFECTIVENESS, AN OBSERVATIONAL COHORT STUDY OF 1.5 MILLION PATIENTS
Guy Hazan, Or Duek, Hillel Alapi, Huram Mok, Alex Ganninger, Elaine Ostendorf, Carrie Gierasch, Gabriel Chodick, David Greenberg, Jeffrey Haspel |
Journal of Clinical Investigation | 2023 |
Immunological and inflammatory effects of infectious diseases in circadian rhythm disruption and future therapeutic directions
Huang H, Mehta A, Kalmanovich J, Anand A, Bejarano MC, Garg T, Khan N, Tonpouwo GK, Shkodina AD, Bardhan M |
Molecular Biology Reports | 2023 |
The Circadian Biology of Heart Failure
El Jamal N, Lordan R, Teegarden SL, Grosser T, FitzGerald G |
Circulation research | 2023 |
Prevalence and management of sleep disturbance in adults with primary brain tumours and their caregivers: a systematic review.
Martin JA, Hart NH, Bradford N, Naumann F, Pinkham MB, Pinkham EP, Holland JJ |
Journal of Neuro-Oncology | 2023 |
Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement
Knauert MP, Ayas NT, Bosma KJ, Drouot X, Heavner MS, Owens RL, Watson PL, Wilcox ME, Anderson BJ, Cordoza ML, Devlin JW, Elliott R, Gehlbach BK, Girard TD, Kamdar BB, Korwin AS, Lusczek ER, Parthasarathy S, Spies C, Sunderram J, Telias I, Weinhouse GL, Zee PC |
American journal of respiratory and critical care medicine | 2023 |
The role of the circadian rhythms in critical illness with a focus on acute pancreatitis
Waddell H, Stevenson TJ, Mole DJ |
Heliyon | 2023 |
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Cunningham PS, Jackson C, Chakraborty A, Cain J, Durrington HJ, Blaikley JF |
Clinical science (London, England : 1979) | 2023 |
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Yalçin M, Relógio A |
PloS one | 2023 |
Acute and repeated ozone exposures differentially affect circadian clock gene expression in mice
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2023 | |
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The Impact of Immunotherapy on Sleep and Circadian Rhythms in Patients with Cancer
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Circadian misalignment impacts the association of visceral adiposity with metabolic syndrome in adolescents
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Sleep | 2023 |
Macrophage Meets the Circadian Clock: Implication of the Circadian Clock in the Role of Macrophages in Acute Lower Respiratory Tract Infection
K Shirato, S Sato |
Frontiers in Cellular and Infection Microbiology | 2022 |
Night shift work characteristics are associated with several elevated metabolic risk factors and immune cell counts in a cross-sectional study
A Streng, B Loef, M Dollé, G van der Horst, I Chaves, K Proper, L van Kerkhof |
Scientific Reports | 2022 |
The role of circadian clock pathways in viral replication
X Zhuang, R Edgar, J McKeating |
Seminars in Immunopathology | 2022 |
The Importance of Sleep and Circadian Rhythms for Vaccination Success and Susceptibility to Viral Infections
N Schmitz, Y van der Werf, H der Holst |
2022 | |
Malnutrition and Dietary Habits Alter the Immune System Which May Consequently Influence SARS-CoV-2 Virulence: A Review
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International journal of molecular sciences | 2022 |
Targeting Nuclear Receptors for TH17-Mediated Inflammation: REV-ERBerations of Circadian Rhythm and Metabolism.
Mosure SA, Wilson AN, Solt LA |
Immunometabolism | 2022 |
Comparison of sleep quality among COVID-19 patients and non-COVID-19 population in Pakistan: A cross sectional study during the COVID-19 pandemic
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Annals of Medicine and Surgery | 2022 |
Time of day as a critical variable in biology
Nelson RJ, Bumgarner JR, Liu JA, Love JA, Meléndez-Fernández OH, Becker-Krail DD, Walker WH II, Walton JC, DeVries AC, Prendergast BJ |
BMC Biology | 2022 |
Circadian clocks of the kidney: function, mechanism, and regulation
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Frontiers in physiology | 2022 |
Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1.
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Immunology | 2022 |
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Nutrients | 2022 |
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Environmental Science and Pollution Research | 2022 |
Disruption of cellular immune response among male rotating night shift workers in Spain– The HORMONIT study
Harding BN, Aguilar R, Espinosa A, Castaño-Vinyals G, Papantoniou K, Navarrete JM, Such Faro P, Torrejón A, Dobaño C, Moncunill G, Kogevinas M |
Frontiers in immunology | 2022 |
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World Journal of Gastroenterology | 2022 |
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Adkins AM, Wellman LL, Sanford LD |
2022 | |
Preliminary evidence that daily light exposure enhances the antibody response to influenza vaccination in patients with dementia
Münch M, Goldbach R, Zumstein N, Vonmoos P, Scartezzini JL, Wirz-Justice A, Cajochen C |
2022 | |
Chronovaccination: Harnessing circadian rhythms to optimize immunisation strategies.
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Insights about circadian clock in glioma: From molecular pathways to therapeutic drugs.
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CNS Neuroscience & Therapeutics | 2022 |
The Association of Time of Day of ChAdOx1 nCoV-19 Vaccine Administration With SARS-CoV-2 Anti-Spike IgG Antibody Levels: An Exploratory Observational Study
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Journal of Biological Rhythms | 2022 |
When the clock ticks wrong with COVID‐19
Papagerakis S, Said R, Ketabat F, Mahmood R, Pundir M, Lobanova L, Guenther G, Pannone G, Lavender K, McAlpin BR, Moreau A, Chen X, Papagerakis P |
Clinical and Translational Medicine | 2022 |
Verification, analytical validation and clinical validation (V3) of wearable dosimeters and light loggers
Spitschan M, Smolders K, Vandendriessche B, Bent B, Bakker JP, Rodriguez-Chavez IR, Vetter C |
2022 | |
Somatovisceral Convergence in Sleep-Wake Cycle: Transmitting Different Types of Information via the Same Pathway
Levichkina E, Pigareva ML, Limanskaya A, Pigarev IN |
2022 | |
The Glymphatic System: A Novel Component of Fundamental Neurobiology
LM Hablitz, M Nedergaard |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2021 |
The Exposome and Immune Health in Times of the COVID-19 Pandemic
J Morales, P Valenzuela, A Castillo-García, J Butragueño, D Jiménez-Pavón, P Carrera-Bastos, A Lucia |
Nutrients | 2021 |
COVID-19: Sleep, Circadian Rhythms and Immunity – Repurposing Drugs and Chronotherapeutics for SARS-CoV-2
A Giri, A Srinivasan, IK Sundar |
Frontiers in neuroscience | 2021 |
Neutrophil Homeostasis and Emergency Granulopoiesis: The Example of Systemic Juvenile Idiopathic Arthritis
B Malengier-Devlies, M Metzemaekers, C Wouters, P Proost, P Matthys |
Frontiers in immunology | 2021 |
Modeling the circadian regulation of the immune system: Sexually dimorphic effects of shift work
SM Abo, AT Layton, A Csikász-Nagy |
PLoS computational biology | 2021 |
Clocks, Viruses, and Immunity: Lessons for the COVID-19 Pandemic
S Sengupta, L Ince, F Sartor, H Borrmann, X Zhuang, A Naik, A Curtis, JA McKeating |
Journal of Biological Rhythms | 2021 |
Circadian rhythms: influence on physiology, pharmacology, and therapeutic interventions
VS Ayyar, S Sukumaran |
Journal of Pharmacokinetics and Pharmacodynamics | 2021 |
Differential effects of COVID-19 lockdowns on well-being: interaction between age, gender and chronotype
S Oved, M Mofaz, A Lan, H Einat, N Kronfeld-Schor, D Yamin, E Shmueli |
Journal of The Royal Society Interface | 2021 |
Mathematical modeling of mammalian circadian clocks affecting drug and disease responses
PD Mavroudis, WJ Jusko |
Journal of Pharmacokinetics and Pharmacodynamics | 2021 |
Very-Short-Term Sleep Deprivation Slows Early Recovery of Lymphocytes in Septic Patients
Y Zhang, Y Wu, D Xu, P Xiao, B Xie, H Huang, Y Shang, S Yuan, J Zhang |
Frontiers in Medicine | 2021 |
Sleep duration and napping in relation to colorectal and gastric cancer in the MCC-Spain study
K Papantoniou, G Castaño-Vinyals, A Espinosa, MC Turner, V Martín-Sánchez, D Casabonne, N Aragonés, I Gómez-Acebo, E Ardanaz, JJ Jimenez-Moleon, P Amiano, A Molina-Barceló, J Alguacil, G Fernández-Tardón, JM Huerta, N Hernández-Segura, B Perez-Gomez, J Llorca, J Vidán-Alli, R Olmedo-Requena, L Gil, C Castañon-López, M Pollan, M Kogevinas, V Moreno |
Scientific Reports | 2021 |
RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence
M Kloc, A Uosef, M Villagran, R Zdanowski, JZ Kubiak, J Wosik, RM Ghobrial |
Biology : open access journal | 2021 |
Melatonin as an Add-On Treatment of COVID-19 Infection: Current Status
GM Brown, SR Pandi-Perumal, H Pupko, JL Kennedy, DP Cardinali |
Diseases | 2021 |
Efficacy and Safety of Auricular Acupuncture for the Treatment of Insomnia in Breast Cancer Survivors: A Randomized Controlled Trial
MD Höxtermann, K Buner, H Haller, W Kohl, G Dobos, M Reinisch, S Kümmel, H Cramer, P Voiss |
Cancers | 2021 |
Single and Combinative Impacts of Healthy Eating Behavior and Physical Activity on COVID-19-like Symptoms among Outpatients: A Multi-Hospital and Health Center Survey
MH Nguyen, TT Pham, DN Vu, BN Do, HC Nguyen, TH Duong, KM Pham, LV Pham, TT Nguyen, CQ Tran, QH Nguyen, TM Hoang, KV Tran, TT Duong, SH Yang, CH Bai, TV Duong |
Nutrients | 2021 |
Sleep, Circadian Health and Melatonin for Mitigating COVID-19 and Optimizing Vaccine Efficacy
RU Lee, GL Glickman |
Frontiers in neuroscience | 2021 |
Physiologic Response to the Pfizer-BioNTech COVID-19 Vaccine Measured Using Wearable Devices: Prospective Observational Study
AG Hajduczok, KM DiJoseph, B Bent, AK Thorp, JB Mullholand, SA MacKay, S Barik, JJ Coleman, CI Paules, A Tinsley |
2021 | |
Tryptophan: A Unique Role in the Critically Ill
M Kanova, P Kohout |
International journal of molecular sciences | 2021 |
Cellular Calcium Levels Influenced by NCA-2 Impact Circadian Period Determination in Neurospora
B Wang, X Zhou, SA Gerber, JJ Loros, JC Dunlap, R Fischer |
mBio | 2021 |
The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses
C Jacques, M Chatelais, K Fekir, L Fauconnier, M Mellier, D Togbe, I Floris |
International journal of molecular sciences | 2021 |
Postnatal Cytokine Trajectories in Very Preterm Infants
M Nist, A Shoben, T Harrison, D Steward, R Pickler |
Western Journal of Nursing Research | 2021 |
Five important preventive measures against exacerbation of coronavirus disease.
Yamamoto K |
2021 | |
Neural Immune Communication in the Control of Host-Bacterial Pathogen Interactions in the Gastrointestinal Tract
V Ramirez, S Swain, K Murray, C Reardon, AR Richardson |
Infection and immunity | 2020 |
Does Sars-Cov-2 threaten our dreams? Effect of quarantine on sleep quality and body mass index
L Barrea, G Pugliese, L Framondi, RD Matteo, D Laudisio, S Savastano, A Colao, G Muscogiuri |
Journal of Translational Medicine | 2020 |
Bringing the cellular clock into understanding lung disease: it’s time, period!
CM Bartman, YS Prakash |
American journal of physiology. Lung cellular and molecular physiology | 2020 |
Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2
AH de Araújo Morais, J de Souza Aquino, JK da Silva-Maia, SH de Lima Vale, BL Maciel, TS Passos |
British Journal of Nutrition | 2020 |
Forging Forward Together: Transforming Scientific Practice to Accelerate Scientific Progress
KL Hall |
Annals of Behavioral Medicine | 2020 |
Diurnal rhythms across the human dorsal and ventral striatum
KD Ketchesin, W Zong, MA Hildebrand, ML Seney, KM Cahill, MR Scott, VG Shankar, JR Glausier, DA Lewis, GC Tseng, CA McClung |
Proceedings of the National Academy of Sciences | 2020 |
The spleen mediates chronic sleep restriction-mediated enhancement of LPS-induced neuroinflammation, cognitive deficits, and anxiety-like behavior
D Xu, Y Zhang, B Xie, H Yao, Y Yuan, S Yuan, J Zhang |
Aging | 2020 |
Mediators of Host–Microbe Circadian Rhythms in Immunity and Metabolism
K Frazier, M Frith, D Harris, VA Leone |
Biology : open access journal | 2020 |
The Impact of Obesity and Lifestyle on the Immune System and Susceptibility to Infections Such as COVID-19
DL de Frel, DE Atsma, H Pijl, JC Seidell, PJ Leenen, WA Dik, EF van Rossum |
Frontiers in Nutrition | 2020 |
Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients?
DP Cardinali, GM Brown, SR Pandi-Perumal |
Diseases | 2020 |
Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration
DP Cardinali, GM Brown, RJ Reiter, SR Pandi-Perumal |
2020 | |
The Generalized Adaptation Account of Autism
C Gernert, P Falkai, CM Falter-Wagner |
Frontiers in neuroscience | 2020 |
Poor-sleep is associated with slow recovery from lymphopenia and an increased need for ICU care in hospitalized patients with COVID-19: A retrospective cohort study
J Zhang, D Xu, B Xie, Y Zhang, H Huang, H Liu, H Chen, Y Sun, Y Shang, K Hashimoto, S Yuan |
Brain, Behavior, and Immunity | 2020 |
Nowhere to hide: The significant impact of coronavirus disease 2019 (COVID-19) measures on elite and semi-elite South African athletes
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Journal of Science and Medicine in Sport | 2020 |
Distinguishing Intrapulmonary Immune Cells from Intravascular Immune Cell Populations: the Intrajugular Approach
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Journal of visualized experiments : JoVE | 2020 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |