When Should the Immune Clock Be Reset?

Lévi, Françis; Canon, C; Dipalma, Mario; Florentin, I.; Misset, Jean-Louis

doi:10.1111/j.1749-6632.1991.tb27251.x

Cited by 59 publications

(9 citation statements)

References 39 publications

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“…lymphocyte proliferation, antigen presentation, and cytokine gene expression) (Arjona and Sarkar, 2005, 2006; Levi et al, 1991; Maestroni and Conti, 1996). It is intriguing to speculate that aspects of the host innate immune system are under circadian regulation in order to anticipate the time of day when a pathogenic encounter is most likely to occur.…”

Section: Discussionmentioning

confidence: 99%

Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells

Silver¹,

Arjona²,

Hughes³

et al. 2012

Brain, Behavior, and Immunity

142

110

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In mammals, circadian and daily rhythms influence nearly all aspects of physiology, ranging from behavior to gene expression. Functional molecular clocks have been described in the murine spleen and splenic NK cells. The aim of our study was to investigate the existence of molecular clock mechanisms in other immune cells. Therefore, we measured the circadian changes in gene expression of clock genes (Per1, Per2, Bmal1, and Clock) and clock-controlled transcription factors (Rev-erbα and Dbp) in splenic enriched macrophages, dendritic cells, and B cells in both mice entrained to a light-dark cycle and under constant environmental conditions. Our study reveals the existence of functional molecular clock mechanisms in splenic macrophages, dendritic cells, and B cells.

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Section: Discussionmentioning

confidence: 99%

Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells

Silver¹,

Arjona²,

Hughes³

et al. 2012

Brain, Behavior, and Immunity

142

110

View full text Add to dashboard Cite

show abstract

“…[17][18][19][20] There is a growing body of evidence that circadian rhythms also govern immunoreactions such as antigen presentation, lymphocyte proliferation, and cytokine expression. [21][22][23] More recently, diurnal expression of granzyme B and perforin in natural killer (NK) cells was observed in vivo.…”

Section: -6)mentioning

confidence: 99%

“…[21][22][23] More recently, diurnal expression of granzyme B and perforin in natural killer (NK) cells was observed in vivo. 12) These circadian variations in the immune system are likely to be regulated by molecular clocks for the following reasons.…”

mentioning

confidence: 99%

Characterization of the Molecular Clock in Mouse Peritoneal Macrophages

Hayashi

Shimba

Tezuka

2007

Biological & Pharmaceutical Bulletin

175

157

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Circadian rhythm is observed in most, if not all, of physiological functions, including metabolism, cell growth, etc. 1-6)The master pacemaker of circadian rhythm resides in the suprachiasmatic nucleus (SCN) of the hypothalamus and coordinates autonomous peripheral clocks located in organs such as the liver and kidney. [7][8][9][10][11][12] The molecular clock is composed of transcriptional feedback loops in organisms ranging from cyanobacteria to humans. Two transcription factors, the brain and muscle Arnt-like protein-1 (BMAL1; also referred to as MOP3 or Arnt3) and CLOCK, play central roles in the regulation of circadian rhythms.13-16) BMAL1 and CLOCK form a heterodimer and drive transcription from E-box elements found in the promoter of circadian-responsive genes, including period (Per)1 and cryptochrome (Cry). After translation of the Per and Cry proteins, the Per/Cry complex translocates to the nucleus, where it inhibits gene expression driven by BMAL1 and CLOCK. [17][18][19][20] There is a growing body of evidence that circadian rhythms also govern immunoreactions such as antigen presentation, lymphocyte proliferation, and cytokine expression. [21][22][23] More recently, diurnal expression of granzyme B and perforin in natural killer (NK) cells was observed in vivo.12) These circadian variations in the immune system are likely to be regulated by molecular clocks for the following reasons. First, RNAi-mediated Per2 knockdown caused a significant decrease of granzyme B and perforin levels in the rat-derived NK cell line RNK16.24) Second, Per2-deficient mice were more resistant to lipopolysaccharide (LPS)-induced endotoxic shock than wild-type mice.25) Also, the levels of the proinflammatory cytokines gamma interferon (IFN) and interleukin (IL)-1beta were dramatically decreased in Per2 Ϫ/Ϫ mice following LPS challenge, while the productions of tumor necrosis factor alpha (TNFa), IL-6, and IL-10 were approximately equal to those in wild-type mice.25) Furthermore, studies using BMAL1-deficient mice revealed that BMAL1 is required for B cell development. 26)Although several studies have shown that the immunoreactions and onset of the inflammatory diseases exhibit circadian variation, 27-30) the molecular details of the circadian rhythms in macrophages are still poorly understood. Therefore, in this study, we attempted to characterize circadian gene expression in mice peritoneal macrophages. We found that the expression of several clock genes such as BMAL1 exhibited daily oscillations in resident peritoneal macrophages. The expression of inflammatory factors such as monocyte chemoattractant protein-1 (MCP-1/JE) exhibited robust circadian rhythms. Suppression of BMAL1 expression by an RNAi technique lowered the nuclear factor-kappa B (NF-kB) activity followed by down-regulation of MCP-1/JE mRNA expression in RAW264.7 macrophage cells. Macrophages are known to play essential roles in immunoreactions and pathogenesis of atherosclerosis and arthropathy. 31,32) Consequently, these results may provide further insight ...

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“…It is well known that the immune response to antigen differs quantitatively and qualitatively depending upon the duration of exposure to light [9,23]. In animal models, manipulating the day length modifies immunity toward either enhancement (shorter photoperiod) or relative depression (longer photoperiod), even during the winter [3,24-26].…”

Section: Discussionmentioning

confidence: 99%

Light and the outcome of the critically ill: an observational cohort study

et al. 2012

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IntroductionLight before and during acute illness has been associated with both benefit and harm in animal models and small human studies. Our objective was to determine the associations of light duration (photoperiod) and intensity (insolation) before and during critical illness with hospital mortality in ICU patients. Based on the 'winter immunoenhancement' theory, we tested the hypothesis that a shorter photoperiod before critical illness is associated with improved survival.MethodsWe analyzed data from 11,439 patients admitted to 8 ICUs at the University of Pittsburgh Medical Center between June 30, 1999 and July 31, 2004. Daily photoperiod and insolation prior to and after ICU admission were estimated for each patient by using data provided by the United States Naval Observatory and National Aeronautics and Space Administration and direct measurement of light gradient from outside to bedside for each ICU room. Our primary outcome was hospital mortality. The association between light and risk of death was analyzed using multivariate analyses, adjusting for potential confounders, including severity of illness, case mix, and ICU type.ResultsThe cohort had an average APACHE III of 52.9 and a hospital mortality of 10.7%. In total, 128 ICU beds were analyzed; 108 (84%) had windows. Pre-illness photoperiod ranged from 259 to 421 hours in the prior month. A shorter photoperiod was associated with a reduced risk of death: for each 1-hour decrease, the adjusted OR was 0.997 (0.994 to 0.999, p = 0.03). In the ICU, there was near complete (99.6%) degradation of natural light from outside to the ICU bed. Thus, light exposure once in the ICU approached zero; the 24-hour insolation was 0.005 ± 0.003 kWh/m2 with little diurnal variation. There was no association between ICU photoperiod or insolation and mortality.ConclusionsConsistent with the winter immunoenhancement theory, a shorter photoperiod in the month before critical illness is associated with a reduced risk of death. Once in the ICU, patients are exposed to near negligible natural light despite the presence of windows. Further studies are warranted to determine the underlying mechanisms and whether manipulating light exposure, before or during ICU admission, can enhance survival.

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When Should the Immune Clock Be Reset?

Cited by 59 publications

References 39 publications

Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells

Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells

Characterization of the Molecular Clock in Mouse Peritoneal Macrophages

Light and the outcome of the critically ill: an observational cohort study

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