Circadian Oscillations of Clock Genes, Cytolytic Factors, and Cytokines in Rat NK Cells

Arjona, Álvaro; Sarkar, Dipak K.

doi:10.4049/jimmunol.174.12.7618

Cited by 192 publications

(160 citation statements)

References 80 publications

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“…The expression of NK cells oscillates throughout a 24 hour period, with peak expression occurring in the early morning [4]. Numerous other components of the immune system, such as T-helper, T-suppressor and splenic B-cells, also display a 24-hour oscillation similar to that of the NK cells [5].…”

Section: Possible Mechanisms: Clock-controlled Immune Functionmentioning

confidence: 96%

“…Despite tremendous efforts to improve our understanding of this cancer, its etiology remains largely unknown with the only well-established risk factor for NHL being immune deregulation [2]. Given that several essential components of the innate immune system are influenced by the 24-hour circadian rhythm [3][4][5], we speculate that circadian disruption might play a role in lymphomagenesis by detrimentally affecting immune activity. Furthermore, we hypothesize that genetic variation in genes responsible for maintaining circadian rhythm might act as a novel panel of biomarkers associated with an individual's susceptibility to NHL.…”

Section: Introductionmentioning

confidence: 99%

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Clock-cancer connection in non-Hodgkin’s lymphoma

Zhu

Zheng

2008

Medical Hypotheses

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The universal 24-hour circadian clock has a profound impact on many daily biological processes. Disturbance of circadian rhythms has been implicated in the etiologies of many chronic illnesses, including cancer; with correlations most profoundly found among hormone-related breast and prostate cancers. Given the fact that circadian disruption can cause immune deregulation, which is so far the only established risk factor for non-Hodgkin's lymphoma (NHL), we hypothesize that altered circadian rhythms due to environmental factors and/or genetic variations in genes responsible for maintaining circadian rhythms may result in the deregulation of clock-associated biological processes such as immune responses and activities, and consequently influence an individual's risk of developing NHL. Our recent findings provided the first molecular epidemiological evidence linking a major circadian gene to NHL and warrant further investigation. Confirmation of this hypothesis will further add to our understanding of the role of the circadian clock in lymphomagenesis and facilitate the development of novel risk and prognostic biomarkers for NHL.

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Section: Possible Mechanisms: Clock-controlled Immune Functionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Clock-cancer connection in non-Hodgkin’s lymphoma

Zhu

Zheng

2008

Medical Hypotheses

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“…The existence of such oscillators has been supported by the expression of clock genes in blood cells of both humans (22)(23)(24) and rodents (13,25,26) as well as in lymphoid organs such as bone marrow, thymus, spleen, and lymph nodes (LNs) (13,25,(27)(28)(29)(30)(31). What is the functional consequence of these immune clocks?…”

mentioning

confidence: 99%

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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“…Chronic inflammation is one of the important pathogenic features of these diseases, which prompted us to hypothesize that circadian clock components may play a role in the regulation of inflammation. Moreover, recent evidence demonstrated that major players in immune function, such as spleen, lymph node, and macrophage and natural killer (NK) cells, contain a cell-autonomous circadian clock (8)(9)(10). Moreover, secretion of cytokines, TNF-α and IL-6 has been reported to display circadian oscillation in macrophages, where ∼8% of transcriptome is under circadian regulation (10).…”

mentioning

confidence: 99%

Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines

Narasimamurthy

Hatori

Nayak

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

344

264

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Chronic sleep deprivation perturbs the circadian clock and increases susceptibility to diseases such as diabetes, obesity, and cancer. Increased inflammation is one of the common underlying mechanisms of these diseases, thus raising a hypothesis that circadianoscillator components may regulate immune response. Here we show that absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. We observed a constitutive NF-κB and protein kinase A (PKA) signaling activation in Cry1 −/− ; Cry2 −/− cells. We further demonstrate that increased phosphorylation of p65 at S276 residue in Cry1 −/− ;Cry2 −/− cells is due to increased PKA signaling activity, likely induced by a significantly high basal level of cAMP, which we detected in these cells. In addition, we report that CRY1 binds to adenylyl cyclase and limits cAMP production. Based on these data, we propose that absence of CRY protein(s) might release its (their) inhibition on cAMP production, resulting in elevated cAMP and increased PKA activation, subsequently leading to NF-κB activation through phosphorylation of p65 at S276. These results offer a mechanistic framework for understanding the link between circadian rhythm disruption and increased susceptibility to chronic inflammatory diseases.biological clock | immune system I n response to the rotation of the earth, many of the mammalian physiological processes such as sleep-wake cycle and feeding pattern undergo an ∼24-h oscillation referred as the circadian clock. Circadian oscillation helps organisms anticipate and adapt to predictable daily changes in the environment. The hypothalamic suprachiasmatic nucleus (SCN) functions as a master circadian oscillator, which controls behaviors. At molecular level, the circadian oscillator is based on a cell-autonomous transcription-translation feedback loop, in which transcriptional activators circadian locomotor output cycles kaput (CLOCK)/brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like (BMAL)1 activate the expression of Cryptochrome (Cry) and Period (Per), in turn their protein products repress BMAL1 and CLOCK activity, thus producing Cry and Per expression rhythms (1, 2). Reverse orientation c-erb (REV-ERB)s and RAR-related orphan receptor (ROR)s also participate in the rhythmic transcriptional activity of the molecular oscillator (3). Molecular components of the circadian clock network are conserved in the SCN and also in peripheral cells. The oscillator uses direct and indirect mechanisms to impose rhythms and regulate several physiological processes, such as rest-activity cycle, endocrine system, and metabolism (4).Sleep loss or chronic sleep deprivation disrupts the circadian rhythm. It has been reported that people exposed to constant circadian disruption, such as shift-workers, show increased incidence of chronic diseases such as diabetes, obesity, and also cancer (5-7). Chronic inflammation is one of the important pathogenic features of these di...

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Circadian Oscillations of Clock Genes, Cytolytic Factors, and Cytokines in Rat NK Cells

Cited by 192 publications

References 80 publications

Clock-cancer connection in non-Hodgkin’s lymphoma

Clock-cancer connection in non-Hodgkin’s lymphoma

Circadian Variation of the Response of T Cells to Antigen

Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines

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