Clock mutation affects circadian regulation of circulating blood cells

Oishi, Katsutaka; Ohkura, Naoki; Kadota, Koji; Kasamatsu, Manami; Shibusawa, Kentaro; Matsuda, Juzo; Machida, Kazuhiko; Horie, Shuichi; Ishida, Norio

doi:10.1186/1740-3391-4-13

Cited by 73 publications

(70 citation statements)

References 33 publications

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“…Yet, a detailed analysis of immune responses of Clock mutant mice has not been reported. The amplitude of leukocyte count rhythms is reduced in the peripheral blood of Clock mutant mice (48,54). Notably, changes in cell numbers are unlikely to explain the proliferation described in this work, as we found no difference in levels of lymphocyte subsets in LNs of Clock mutant versus WT mice.…”

Section: Discussioncontrasting

confidence: 44%

“…These mice display a long freerunning period in DD, and eventually arrhythmicity after 2-3 wk (33). Moreover, in these mutants, the expression of the genes controlled by the CLOCK/BMAL1 dimer is blunted (45)(46)(47), and the amplitude of the corticosterone rhythm is reduced (48) or abolished (46) depending on the genetic background. These mutant mice also display shorter total sleep duration and reduced recovery sleep after sleep deprivation (49).…”

Section: Discussionmentioning

confidence: 99%

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Circadian Variation of the Response of T Cells to Antigen

Fortier¹,

Rooney²,

Dardente³

et al. 2011

The Journal of Immunology

156

171

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Circadian clocks regulate many important aspects of physiology, and their disturbance leads to various medical conditions. Circadian variations have been found in immune system variables, including daily rhythms in circulating WBC numbers and serum concentration of cytokines. However, control of immune functional responses by the circadian clock has remained relatively unexplored. In this study, we show that mouse lymph nodes exhibit rhythmic clock gene expression. T cells from lymph nodes collected over 24 h show a circadian variation in proliferation after stimulation via the TCR, which is blunted in Clock gene mutant mice. The tyrosine kinase ZAP70, which is just downstream of the TCR in the T cell activation pathway and crucial for T cell function, exhibits rhythmic protein expression. Lastly, mice immunized with OVA peptide-loaded dendritic cells in the day show a stronger specific T cell response than mice immunized at night. These data reveal circadian control of the Ag-specific immune response and a novel regulatory mode of T cell proliferation, and may provide clues for more efficient vaccination strategies.

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Section: Discussioncontrasting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

Circadian Variation of the Response of T Cells to Antigen

Fortier¹,

Rooney²,

Dardente³

et al. 2011

The Journal of Immunology

156

171

View full text Add to dashboard Cite

show abstract

“…Interestingly, the blood O 2 level in the dark period (zeitgeber time [ZT] 12-ZT13) was higher (Supplemental Figure 1, B and C), compared with those in the light period (ZT5-ZT6). Total Hb was higher in the light period than the dark period (Supplemental Figure 1D), an observation that is consistent with a previous report (23). These results show that blood O 2 levels correlated diurnal changes in EE.…”

Section: Resultssupporting

confidence: 81%

Red blood cell β-adrenergic receptors contribute to diet-induced energy expenditure by increasing O2 supply

Kim

Fan

Akhmedov³

et al. 2017

JCI Insight

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“…10,11) Corticosteroids are also related to the numbers of plasma lymphocytes by causing some lymphocyte efflux from the vasculature and retention in the lymphatic circulation.…”

Section: Discussionmentioning

confidence: 99%

“…The decrease in the number of lymphocytes number after the CS concentration peaks reflects a decrease in the number of WBCs in mice. 10) Therefore, the increased plasma CS concentration might contribute to the low WBCs count in the C3H/HeN strain. Thus, the CS-induced changes in CAMs expressions in leukocytes or endothelial cells might be involve in the low number of WBCs in C3H/HeN mice.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of Circadian Variation in Numbers of Peripheral Blood Cells among Mouse Strains: Unique Feature of C3H/HeN Mice

Ohkura

Oishi

Sekine

et al. 2007

Biological & Pharmaceutical Bulletin

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Circadian variations in circulating blood cells have been recognized in various species.1) Periodic changes in the numbers of circulating cells in the peripheral blood might be the result of multiple factors such as the distribution between the circulating and marginal cell compartment among the tissues and organs of the body, influx from storage sites, cell proliferation, release of cells formed de novo into the circulation, as well as cell destruction and removal.2) The underlying mechanisms of circadian changes in circulating blood cells have not been fully elucidated, but the numbers of monocytes, natural killer (NK) cells, T and B cells, red blood cells fluctuate in a circadian manner.3-6) Thus, to study the hematological aspect such as immune function, anti-tumor activities and hematopoiesis, circadian rhythms in the numbers of circulating blood cells must be considered.Animal models are revolutionary tools for chronobiological studies that provide some obvious benefits. Experiments can be conducted in animals that would not be feasible in the humans, and genetic background as well as most environmental factors can be controlled. Such models have served as powerful tools for understanding the circadian rhythms of various biological parameters. However, the effect of the difference of genetic backgrounds on circadian rhythmicity of peripheral blood cells has not been studied in detail.In most inbred mouse strains except for the C3H, a genetic defect in the rate-limiting enzyme N-acetyl transferase blocks the production of the pineal melatonin.7) Interestingly, the number of circulating WBCs is sensitive to photoperiod via melatonin-mediated effects.8) Therefore, the initial goal of the present study was to test the hypothesis that the absence of a circadian melatonin rhythm in the circulation affects the circadian profile of the circulating blood cells.On the other hand, genetically engineered animals, such as transgenic and knockout mice are indispensable to elucidating the molecular mechanisms of many physiological functions. To breed knockout mice for investigations of these functions, parental or backcrossed strains must be appropriately selected. Although many knockout mouse lines have been generated and many physiological functions have been observed in vivo, the effect of the genetic background of strains has not always been considered. Consequently, a comparison of numbers of blood cells and their circadian rhythms in several strains of mice should provide useful information for experimentation using these mouse models.In this study, we observed changes in the numbers of circulating WBCs and RBCs in Jcl:ICR, BALB/cA, C57BL/6J and C3H/HeN mice throughout the day to obtain fundamental information about strain differences in the number of peripheral circulating blood cells and their circadian rhythms. We also examined the plasma concentrations of CS and EPO in these strains of mice that related to the numbers of circulating WBSs and RBCs, respectively. The present observations should provide basic info...

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Clock mutation affects circadian regulation of circulating blood cells

Abstract: Background: Although the number of circulating immune cells is subject to high-amplitude circadian rhythms, the underlying mechanisms are not fully understood.

Cited by 73 publications

References 33 publications

Circadian Variation of the Response of T Cells to Antigen

Circadian Variation of the Response of T Cells to Antigen

Red blood cell β-adrenergic receptors contribute to diet-induced energy expenditure by increasing O2 supply

Comparative Study of Circadian Variation in Numbers of Peripheral Blood Cells among Mouse Strains: Unique Feature of C3H/HeN Mice

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