A matter of time: study of circadian clocks and their role in inflammation

Carter, Stuart J.; Durrington, Hannah J.; Gibbs, Julie; Blaikley, John; Loudon, A. S. I.; Ray, David; Sabroe, Ian

doi:10.1189/jlb.3ru1015-451r

Cited by 70 publications

(52 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mice show differential resistance against infection at different times of the day. Inflammation, immune resistance, and the severity of autoimmune diseases are also found to vary throughout the day in a rhythmic manner (Carter et al, 2016; Curtis et al, 2014; Cutolo, 2012; Gibbs and Ray, 2013). The chronic disruption of circadian rhythms, including sleep deprivation, shift work, and jet lag can precipitate disease even in healthy individuals and exacerbate existing diseases, particularly inflammatory conditions (Ranjbaran et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila

Terry

Fejér

et al. 2017

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

The circadian clock is a transcriptional/translational feedback loop that drives the rhythmic expression of downstream mRNAs. Termed “clock-controlled genes,” these molecular outputs of the circadian clock orchestrate cellular, metabolic, and behavioral rhythms. As part of our on-going work to characterize key upstream regulators of circadian mRNA expression, we have identified a novel clock-controlled gene in Drosophila melanogaster, Achilles (Achl), which is rhythmic at the mRNA level in the brain and which represses expression of anti-microbial peptides in the immune system. Achilles knock-down in neurons dramatically elevates expression of crucial immune response genes, including IM1 (Immune induced molecule 1), Mtk (Metchnikowin), and Drs (Drosomysin). As a result, flies with knocked-down Achilles expression are resistant to bacterial challenges. Meanwhile, no significant change in core clock gene expression and locomotor activity is observed, suggesting that Achilles influences rhythmic mRNA outputs rather than directly regulating the core timekeeping mechanism. Notably, Achilles knock-down in the absence of immune challenge significantly diminishes the fly’s overall lifespan, indicating a behavioral or metabolic cost of constitutively activating this pathway. Together, our data demonstrate that (1) Achilles is a novel clock-controlled gene that (2) regulates the immune system, and (3) participates in signaling from neurons to immunological tissues.

show abstract

Section: Introductionmentioning

confidence: 99%

Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila

Terry

Fejér

et al. 2017

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

show abstract

“…Accumulating clinical and experimental observations supporting the rhythmic nature of immune functions 42,51,52 have raised the issue whether leukocytes possess a molecular oscillator. In 2003, Boivin and colleagues demonstrated that expression of clock genes in human peripheral blood mononuclear cells displays a daily rhythm.…”

Section: Various Leukocytesmentioning

confidence: 99%

Circadian regulation of neutrophils: Control by a cell‐autonomous clock or systemic factors?

Ella

Mócsai

Káldi

2018

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…Together with the shared involvement of circadian disruptions, both MDD and AD have been associated with altered inflammatory states (30, 31). The pro-inflammatory cytokine interleukin 6 (IL-6) (32), which is linked to circadian clock-related inflammation (33), is considered to play a central role in the pathophysiology of MDD and AD (30, 31, 34–39). Indeed, IL-6 has been proposed as a molecular bridge between circadian and inflammatory processes in a chronobiological animal model of depression (40) and is implicated in circadian rhythmicity (41) and in the circadian regulation of sleep drive (42, 43).…”

Section: Introductionmentioning

confidence: 99%

Disrupted Ultradian Activity Rhythms and Differential Expression of Several Clock Genes in Interleukin-6-Deficient Mice

et al. 2017

View full text Add to dashboard Cite

The characteristics of the cycles of activity and rest stand out among the most intensively investigated aspects of circadian rhythmicity in humans and experimental animals. Alterations in the circadian patterns of activity and rest are strongly linked to cognitive and emotional dysfunctions in severe mental illnesses such as Alzheimer’s disease (AD) and major depression (MDD). The proinflammatory cytokine interleukin 6 (IL-6) has been prominently associated with the pathogenesis of AD and MDD. However, the potential involvement of IL-6 in the modulation of the diurnal rhythms of activity and rest has not been investigated. Here, we set out to study the role of IL-6 in circadian rhythmicity through the characterization of patterns of behavioral locomotor activity in IL-6 knockout (IL-6 KO) mice and wild-type littermate controls. Deletion of IL-6 did not alter the length of the circadian period or the amount of locomotor activity under either light-entrained or free-running conditions. IL-6 KO mice also presented a normal phase shift in response to light exposure at night. However, the temporal architecture of the behavioral rhythmicity throughout the day, as characterized by the quantity of ultradian activity bouts, was significantly impaired under light-entrained and free-running conditions in IL-6 KO. Moreover, the assessment of clock gene expression in the hippocampus, a brain region involved in AD and depression, revealed altered levels of cry1, dec2, and rev-erb-beta in IL-6 KO mice. These data propose that IL-6 participates in the regulation of ultradian activity/rest rhythmicity and clock gene expression in the mammalian brain. Furthermore, we propose IL-6-dependent circadian misalignment as a common pathogenetic principle in some neurodegenerative and neuropsychiatric disorders.

show abstract

A matter of time: study of circadian clocks and their role in inflammation

Cited by 70 publications

References 114 publications

Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila

Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila

Circadian regulation of neutrophils: Control by a cell‐autonomous clock or systemic factors?

Disrupted Ultradian Activity Rhythms and Differential Expression of Several Clock Genes in Interleukin-6-Deficient Mice

Contact Info

Product

Resources

About