Cortisol and epinephrine control opposing circadian rhythms in T cell subsets

Dimitrov, Stoyan; Benedict, Christian; Heutling, Dennis; Westermann, Jürgen; Born, Jan; Lange, Tanja

doi:10.1182/blood-2008-11-190769

Cited by 290 publications

(323 citation statements)

References 49 publications

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“…In line with previous studies (15)(16)(17)(18), we demonstrated that subjects living under a day-oriented schedule expressed rhythms of circulating T lymphocyte and monocyte counts that peaked during the night and day, respectively. With four 24-h cycles of night shift, the phases of these rhythms remained similar to those observed at baseline and, therefore, were not aligned to the shifted sleep-wake/feeding cycle.…”

Section: Discussionsupporting

confidence: 79%

“…Hence, changing the timing of sleep and feeding for four consecutive days does not modify the rhythm of circulating T lymphocytes and monocytes. Studies in humans indicated that the number of circulating T cells is regulated by the central clock via glucocorticoid signaling (18,36). The present study, as well as previous studies, shows that, for most night shift workers, central clock-derived signals, such as melatonin and cortisol rhythms, do not spontaneously shift in response to night shift (39,56).…”

Section: Discussionsupporting

confidence: 56%

“…6). On one hand, as the result of the absence of a phase shift in response to night shift for immune cell counts rhythms and melatonin (the current study), as well as for cortisol rhythms (56), we propose that immune cell distribution between blood and tissues is primarily regulated by the central clock, via neuronal and/or humoral regulators (e.g., cortisol) acting on adhesion molecules and chemokines (18,37,57). On the other hand, due to the presence of a phase shift in cytokine-secretion rhythms in response to night shift, we infer that the sensitivity of immune cells to stimuli (e.g., LPS or PHA in our study) or their capacity to produce cytokines in response to these stimuli is dependent on the local clocks intrinsic to these immune cells.…”

Section: Discussionmentioning

confidence: 99%

“…The rhythmic functions, such as cytokine production, seem to be under the control of the immune clocks (19,25,28), whereas the number of circulating WBCs appears to be controlled by the central clock via humoral and neuronal signaling (18,36,37). It is hypothesized that immune clocks are able to gate the integration of central clock's signals to limit or reinforce their effects at certain times of day (14).…”

mentioning

confidence: 99%

“…Among them, the innate and adaptive immune systems were shown to display daily rhythms in rodents and humans (14). This includes rhythms in cell counts in the blood (15)(16)(17)(18) and peripheral lymphoid organs (19), lymphocyte proliferation (20), cytokine levels in the blood (21)(22)(23)(24), and following ex vivo stimulation with various stimuli (16,19,(25)(26)(27)(28).…”

mentioning

confidence: 99%

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Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans

Cuesta

Boudreau

Dubeau-Laramée

et al. 2016

The Journal of Immunology

112

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Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1β, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5–6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep–wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans

Cuesta

Boudreau

Dubeau-Laramée

et al. 2016

The Journal of Immunology

112

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Diurnal Variations in Immunity

Zhao

Chen

2019

Encyclopedia of Life Sciences

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Many aspects of immune systems show diurnal variations depending on environmental and physical conditions, which are driven by internal circadian biological clocks and have been widely observed. Diurnal oscillations of immune mediators coordinate with the activity of the immune system, possibly allowing the host to anticipate and handle microbial threats more efficiently. These oscillations may also contribute to stimulation of organ proliferation, recovery and the clearance of potentially harmful cellular elements from the circulation. In addition, abnormal diurnal oscillations in immune system are associated with inflammation response induced by disorders or dysregulation of behaviour, physiology, metabolism, disease symptoms or response to drugs treatment. The overview of diurnal variations perspective of human immune system may provide novel strategies in clinical treatment. Key Concepts Diurnal variations in immunity exist widely in nature. Diurnal variations in immunity show differences between species, for example mouse and human. Diurnal variations in immunity are regulated by clock genes. Disruptions of circadian oscillations of immune system are closely associated with human diseases. Chrono‐immunotherapeutics should be attracting more attention in clinical treatment.

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Developmental Plasticity of Individual Variation in Stress Responses

Wada

2014

Integrative Organismal Biology

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Cortisol and epinephrine control opposing circadian rhythms in T cell subsets

Cited by 290 publications

References 49 publications

Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans

Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans

Diurnal Variations in Immunity

Developmental Plasticity of Individual Variation in Stress Responses

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