Are Circadian Rhythms the Code of Hypothalamic-Immune Communication? Insights from Natural Killer Cells

Arjona, Álvaro; Sarkar, Dipak K.

doi:10.1007/s11064-007-9501-z

Cited by 50 publications

(41 citation statements)

References 125 publications

(111 reference statements)

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“…The lack of robust diurnality of ex vivo cytokine release in the present study is in contrast to other species (human, rat, mouse) in which diurnal or circadian rhythms of cytokines have been regularly documented (Petrovsky et al, 1994Pollmächer et al, 1996;Arjona and Sarkar, 2008;Keller et al, 2009). It is, however, in line with a report by Murphy et al (2006), who found evidence of an oscillating peripheral clock in an equine fibroblast cell line and adipose tissue, but not in peripheral blood.…”

Section: Time Of Sampling Has No Distinct Effectsupporting

confidence: 84%

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

Schnabel

Steinig

Schuberth

et al. 2015

Veterinary Immunology and Immunopathology

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Section: Time Of Sampling Has No Distinct Effectsupporting

confidence: 84%

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

Schnabel

Steinig

Schuberth

et al. 2015

Veterinary Immunology and Immunopathology

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“…6 and 32 and reviewed in ref. 33), again underlining the pervasiveness of circadian control in the immune system.…”

Section: Discussionmentioning

confidence: 99%

A circadian clock in macrophages controls inflammatory immune responses

Keller¹,

Mazùch²,

Abraham

et al. 2009

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

682

675

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Time of day-dependent variations of immune system parameters are ubiquitous phenomena in immunology. The circadian clock has been attributed with coordinating these variations on multiple levels; however, their molecular basis is little understood. Here, we systematically investigated the link between the circadian clock and rhythmic immune functions. We show that spleen, lymph nodes, and peritoneal macrophages of mice contain intrinsic circadian clockworks that operate autonomously even ex vivo. These clocks regulate circadian rhythms in inflammatory innate immune functions: Isolated spleen cells stimulated with bacterial endotoxin at different circadian times display circadian rhythms in TNF-␣ and IL-6 secretion. Interestingly, we found that these rhythms are not driven by systemic glucocorticoid variations nor are they due to the detected circadian fluctuation in the cellular constitution of the spleen. Rather, a local circadian clock operative in splenic macrophages likely governs these oscillations as indicated by endotoxin stimulation experiments in rhythmic primary cell cultures. On the molecular level, we show that >8% of the macrophage transcriptome oscillates in a circadian fashion, including many important regulators for pathogen recognition and cytokine secretion. As such, understanding the cross-talk between the circadian clock and the immune system provides insights into the timing mechanism of physiological and pathophysiological immune functions.adrenalectomy ͉ LPS ͉ IL-6 ͉ microarray ͉ TNF-␣ A 24-h periodicity in the environment has led to the evolution of molecular circadian clocks in organisms ranging from cyanobacteria to humans. Circadian rhythms display a near 24-h period and persist even in the absence of external timing information. In mammals, a small hypothalamic region, the suprachiasmatic nucleus (SCN), has been identified as the master pacemaker regulating circadian rhythms in physiology, metabolism, and behavior (1). Recent evidence shows that also peripheral organs such as liver, heart, kidney, skin, and even cultured cell lines contain circadian oscillators. Although the SCN probably sets the phase of these peripheral clocks (by as yet unknown means), recent reports implicate peripheral clocks in the regulation of local physiology (2-4). The fundamental mechanism of rhythm generation is cell autonomous and highly conserved in SCN and peripheral cells: Interlocked transcriptional/translational feedback loops involving clock genes, such as Per1-3, Cry1-2, Clock, Bmal1, and Rev-Erb␣ create oscillations on the molecular level (reviewed in ref. 2).In the immune system, many functions and parameters have been described to be time-of-day dependent, e.g., lymphocyte proliferation (5), natural killer (NK) cell activity (6), humoral immune response (7), rhythms in absolute and relative numbers of circulating white blood cells and their subsets (8), cytokine levels (9), and serum cortisol (10) (reviewed in ref. 11). In addition, time-of-day variation in susceptibility to infection (12), cour...

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“…NK cells are programmed to kill syngeneic and allogeneic tumor cells without prior sensitization (Arjona and Sarkar, 2008). However, during normal pregnancy, the cytolytic function of decidual NK cells is substantially reduced.…”

Section: Discussionmentioning

confidence: 99%

Increased CD56+ NK cells and enhanced Th1 responses in human unexplained recurrent spontaneous abortion

Gao¹,

Wang²

2015

Genet. Mol. Res.

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ABSTRACT. Recurrent spontaneous abortion (RSA) is reported to be associated with immune imbalance at the maternal-fetal interface. Immune cells in the decidual tissue are involved in maintaining immune tolerance during pregnancy; however, whether natural killer (NK) and T cells are altered in unexplained RSA (URSA) remains unknown. In this study, we compared the number and percentage of CD56 + NK cells, CD4 + T cells and CD8 + T cells by flow cytometry in 30 URSA patients and 30 normal pregnant controls. We found that there are a higher proportion of CD4 + T cells and CD16 + CD56+ NK cells and a lower number of CD8 + T cells in the decidual tissue of URSA patients compared to normal controls. In addition, the number of T helper type 1 (Th1) cells and the Th1/Th2 ratio were higher in URSA patients compared to normal pregnant controls. In conclusion, our results indicate that the changes in the proportion of local T lymphocyte subsets, NK and Th1 cells, in the maternal-fetal interface may be related to occurrence of URSA.

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Are Circadian Rhythms the Code of Hypothalamic-Immune Communication? Insights from Natural Killer Cells

Cited by 50 publications

References 125 publications

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

Influences of age and sex on leukocytes of healthy horses and their ex vivo cytokine release

A circadian clock in macrophages controls inflammatory immune responses

Increased CD56+ NK cells and enhanced Th1 responses in human unexplained recurrent spontaneous abortion

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