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Abstract

Circadian rhythms, which have long been known to play crucial roles in physiology, are emerging as important regulators of specific immune functions. Circadian oscillations of immune mediators coincide with the activity of the immune system, possibly allowing the host to anticipate and handle microbial threats more efficiently. These oscillations may also help to promote tissue recovery and the clearance of potentially harmful cellular elements from the circulation. This Review summarizes the current knowledge of circadian rhythms in the immune system and provides an outlook on potential future implications.

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Coordinated transcription of key pathways in the mouse by the circadian clock.

Satchidananda Panda, Marina P. Antoch, Brooke H. Miller … (2002)

In mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed approximately 650 cycling transcripts and showed that the majority of these were specific to either the SCN or the liver. Genetic and genomic analysis suggests that a relatively small number of output genes are directly regulated by core oscillator components. Major processes regulated by the SCN and liver were found to be under circadian regulation. Importantly, rate-limiting steps in these various pathways were key sites of circadian control, highlighting the fundamental role that circadian clocks play in cellular and organismal physiology.

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The genetics of mammalian circadian order and disorder: implications for physiology and disease.

Joseph S Takahashi, Hee-Kyung Hong, Caroline Ko … (2008)

Circadian cycles affect a variety of physiological processes, and disruptions of normal circadian biology therefore have the potential to influence a range of disease-related pathways. The genetic basis of circadian rhythms is well studied in model organisms and, more recently, studies of the genetic basis of circadian disorders has confirmed the conservation of key players in circadian biology from invertebrates to humans. In addition, important advances have been made in understanding how these molecules influence physiological functions in tissues throughout the body. Together, these studies set the scene for applying our knowledge of circadian biology to the understanding and treatment of a range of human diseases, including cancer and metabolic and behavioural disorders.

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Regulation of Circadian Behavior and Metabolism by Rev-erbα and Rev-erbβ

Han-keun Cho, Xuan Zhao, Megumi Hatori … (2012)

The circadian clock acts at the genomic level to coordinate internal behavioral and physiologic rhythms via the CLOCK-BMAL transcriptional heterodimer. Although the nuclear receptors REV-ERBα and β have been proposed to form an accessory feedback loop that contributes to clock function 1,2 , their precise roles and importance remain unresolved. To establish their regulatory potential we generated comparative cistromes of both REV-ERB isoforms, which revealed shared recognition at over 50% of their total sites and extensive overlap with the master circadian regulator BMAL1. While Rev-erbα has been shown to directly regulate Bmal1 expression 1,2 , the cistromic analysis reveals a direct connection between Bmal1 and Rev-erbα and β regulatory circuits than previously suspected. Genes within the intersection of the BMAL1, REV-ERBα and REV-ERBβ cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erbα/β function by creating double-knockout mice (DKOs) profoundly disrupted circadian expression of core circadian clock and lipid homeostatic gene networks. As a result, DKOs show strikingly altered circadian wheel-running behavior and deregulated lipid metabolism. These data now ally Rev-erbα/β with Per, Cry and other components of the principal feedback loop that drives circadian expression and suggest a more integral mechanism for the coordination of circadian rhythm and metabolism.

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PubMed ID:: 23391992

PMC ID:: 4090048

DOI:: 10.1038/nri3386

ScienceOpen disciplines: Chemistry

Keywords: Drug Chronotherapy,Adaptive Immunity,physiology,Animals,Blood Cell Count,Chronobiology Disorders,immunology,Circadian Rhythm,Circadian Rhythm Signaling Peptides and Proteins,genetics,Disease Susceptibility,Feedback, Physiological,Gene Expression Regulation,Hormones,Humans,Immune System,Immunity, Humoral,Inflammation,physiopathology,Mammals,Mice,Models, Immunological,Transcription, Genetic

Circadian control of the immune system.

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Abstract

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HLA-G and immune tolerance in pregnancy

Most cited references 50

Coordinated transcription of key pathways in the mouse by the circadian clock.

The genetics of mammalian circadian order and disorder: implications for physiology and disease.

Regulation of Circadian Behavior and Metabolism by Rev-erbα and Rev-erbβ

Author and article information

Journal

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