Watch your clock: it matters for immunotherapy.

Does time of day matter for cancer immunotherapy? Whereas the concept of optimizing the time of treatment is well documented for chemotherapy, whether it applies to immunotherapy, a revolutionizing treatment exploiting the power of immune cells to control tumors, has recently been addressed in a study published in Cell.

Circadian Control of the Response of Macrophages to Plasmodium Spp.-Infected Red Blood Cells.

Malaria is a serious vector-borne disease characterized by periodic episodes of high fever and strong immune responses that are coordinated with the daily synchronized parasite replication cycle inside RBCs. As immune cells harbor an autonomous circadian clock that controls various aspects of the immune response, we sought to determine whether the intensity of the immune response to Plasmodium spp., the parasite causing malaria, depends on time of infection.

Circadian Regulation of Leishmania Parasite Internalisation in Macrophages and Downstream Cellular Events.

Leishmania spp. parasites use macrophages as a host cell during infection. As a result, macrophages have a dual role: clearing the parasite as well as acting as host cells.

The circadian system: A neglected player in neurodevelopmental disorders.

Patients with neurodevelopmental disorders, such as autism spectrum disorder, often display abnormal circadian rhythms. The role of the circadian system in these disorders has gained considerable attention over the last decades. Yet, it remains largely unknown how these disruptions occur and to what extent they contribute to the disorders' development.

The influence of circadian rhythms on CD8 T cell activation upon vaccination: A mathematical modeling perspective.

Circadian rhythms have been implicated in the modulation of many physiological processes, including those associated with the immune system. For example, these rhythms influence CD8 T cell responses within the adaptive immune system. The mechanism underlying this immune-circadian interaction, however, remains unclear, particularly in the context of vaccination.

The environment and the internal clocks: The study of their relationships from prehistoric to modern times.

The origin of biological rhythms goes back to the very beginning of life. They are observed in the animal and plant world at all levels of organization, from cells to ecosystems. As early as the 18th century, plant scientists were the first to explain the relationship between flowering cycles and environmental cycles, emphasizing the importance of daily light-dark cycles and the seasons.

Time of day and circadian disruption influence host response and parasite growth in a mouse model of cerebral malaria.

Malaria is a disease caused by infection with parasite spp. We studied the circadian regulation of host responses to the parasite, in a mouse model of cerebral malaria. The course of the disease was markedly affected by time of infection, with decreased parasitemia and increased inflammation upon infection in the middle of the night.

Clockwork intruders: Do parasites manipulate their hosts' circadian rhythms?

Most organisms have developed circadian clocks to adapt to 24-hour cycles in the environment. These clocks have become crucial for modulating and synchronizing complex behavioral and biological processes. A number of parasites seem to have evolved to take advantage of their hosts' circadian rhythms to favor their own infection and survival.

Peripheral clock gene oscillations are perturbed in neonatal and adult rat offspring raised under adverse limited bedding conditions.

Circadian (24-h) rhythms in the suprachiasmatic nucleus (SCN) are established in utero in rodents, but rhythmicity of peripheral circadian clocks appears later in postnatal development. Since peripheral oscillators can be influenced by maternal feeding and behavior, we investigated whether exposure to the adverse environmental conditions of limited bedding (LB) during postnatal life would alter rhythmicity in the SCN, adrenal gland and liver in neonatal (postnatal day PND10), juvenile (PND28) and adult rats. We also examined locomotor activity in adults.

Behavioral and cellular responses to circadian disruption and prenatal immune activation in mice.

Most individuals with neurodevelopmental disorders (NDDs), including schizophrenia and autism spectrum disorders, experience disruptions in sleep and circadian rhythms. Epidemiological studies indicate that exposure to prenatal infection increases the risk of developing NDDs. We studied how environmental circadian disruption contributes to NDDs using maternal immune activation (MIA) in mice, which models prenatal infection.

Regulation of Cytotoxic CD8+ T Cells by the Circadian Clock.

Most aspects of physiology, including immunity, present 24-h variations called circadian rhythms. In this review, we examine the literature on the circadian regulation of CD8+ T cells, which are important to fight intracellular infections and tumors. CD8+ T cells express circadian clock genes, and ∼6% of their transcriptome presents circadian oscillations.

The Effect of Night Shifts on 24-h Rhythms in the Urinary Metabolome of Police Officers on a Rotating Work Schedule.

Shift workers face an increased risk of metabolic health problems, but the direct metabolic response to working nights is not fully understood. The aim of this study was to investigate the effect of night shifts on the 24-h urinary metabolome of shift workers. Eleven police officers working rotating shifts completed two 24-h laboratory visits that took place before and after they worked 7 consecutive nights.

Deubiquitinases: key regulators of the circadian clock.

All living organisms experience daily environmental cycles and have consequently evolved to synchronize and adapt to this changing environment. Biological processes such as hormonal secretion, body temperature, and sleep follow daily cycles called circadian rhythms that are driven by a molecular clock running in most cells and tissues of the body. This clock is composed of transcriptional-translational negative feedback loops involving clock genes and proteins.

Exposure to Circadian Disruption During Adolescence Interacts With a Genetic Risk Factor to Modify Schizophrenia-relevant Behaviors in a Sex-dependent Manner.

is a gene associated with schizophrenia. Postmortem studies found a reduced expression of in regions associated with schizophrenia in patients' brains. Sandy (Sdy) mice have a loss-of-function mutation in gene, resulting in behavioral deficits and brain changes similar to those seen in patients with schizophrenia.

Chronic Exposure to Dim Light at Night or Irregular Lighting Conditions Impact Circadian Behavior, Motor Coordination, and Neuronal Morphology.

Mistimed exposure to light has been demonstrated to negatively affect multiple aspects of physiology and behavior. Here we analyzed the effects of chronic exposure to abnormal lighting conditions in mice. We exposed mice for 1 year to either: a standard light/dark cycle, a "light-pollution" condition in which low levels of light were present in the dark phase of the circadian cycle (dim light at night, DLAN), or altered light cycles in which the length of the weekday and weekend light phase differed by 6 h ("social jetlag").

The involvement of host circadian clocks in the regulation of the immune response to parasitic infections in mammals.

Circadian rhythms are recurring variations of physiology with a period of ~24 h, generated by circadian clocks located throughout the body. Studies have shown a circadian regulation of many aspects of immunity. Immune cells have intrinsic clock mechanisms, and innate and adaptive immune responses - such as leukocyte migration, magnitude of inflammation, cytokine production and cell differentiation - are under circadian control.

Circadian rhythms in adaptive immunity and vaccination.

Adaptive immunity allows an organism to respond in a specific manner to pathogens and other non-self-agents. Also, cells of the adaptive immune system, such as T and B lymphocytes, can mediate a memory of an encounter with a pathogen, allowing a more efficient response to a future infection. As for other aspects of physiology and of the immune system, the adaptive immune system is regulated by circadian clocks.

Bone adaptation to mechanical loading in mice is affected by circadian rhythms.

Physical forces are critical for successful function of many organs including bone. Interestingly, the timing of exercise during the day alters physiology and gene expression in many organs due to circadian rhythms. Circadian clocks in tissues, such as bone, express circadian clock genes that target tissue-specific genes, resulting in tissue-specific rhythmic gene expression (clock-controlled genes).

Behavioral phenotyping of mice lacking the deubiquitinase USP2.

Ubiquitin specific peptidase 2 (USP2) is a deubiquitinating enzyme expressed almost ubiquitously in the body, including in multiple brain regions. We previously showed that mice lacking USP2 present altered locomotor activity rhythms and response of the clock to light. However, the possible implication of USP2 in regulating other behaviors has yet to be tested.

Altered circadian rhythms in a mouse model of neurodevelopmental disorders based on prenatal maternal immune activation.

Individuals with neurodevelopmental disorders, such as schizophrenia and autism spectrum disorder, exhibit various sleep and circadian rhythm disturbances that often persist and worsen throughout the lifespan. To study the interaction between circadian rhythm disruption and neurodevelopmental disorders, we utilized a mouse model based on prenatal maternal immune activation (MIA). We hypothesized that MIA exposure would lead to impaired circadian locomotor activity rhythms in adult mouse offspring.

The Assessment of Circadian Rhythms Within the Immune System.

In recent years, circadian rhythms have been observed in many aspects of the immune system, both for the innate immunity (the first line of defense against pathogens) and the adaptive immunity (a more specific set of responses, which lead to immune memory). Here, to illustrate principles to be taken into account when working on circadian rhythms in immunology experiments, two protocols will be presented. The first one aims to analyze immune parameters in blood sampled from human subjects at different times over the day: counts of different cell types among the peripheral blood mononuclear cells and cytokine secretion by monocytes and T cells after ex vivo stimulation.

To Ub or not to Ub: Regulation of circadian clocks by ubiquitination and deubiquitination.

Circadian clocks are internal timing systems that enable organisms to adjust their behavioral and physiological rhythms to the daily changes of their environment. These clocks generate self-sustained oscillations at the cellular, tissue, and behavioral level. The rhythm-generating mechanism is based on a gene expression network with a delayed negative feedback loop that causes the transcripts to oscillate with a period of approximately 24 hr.

Are Circadian Disturbances a Core Pathophysiological Component of Schizophrenia?

Schizophrenia is a multifactorial disorder caused by a combination of genetic variations and exposure to environmental insults. Sleep and circadian rhythm disturbances are a prominent and ubiquitous feature of many psychiatric disorders, including schizophrenia. There is growing interest in uncovering the mechanistic link between schizophrenia and circadian rhythms, which may directly affect disorder outcomes.

Daily variations of gut microbial translocation markers in ART-treated HIV-infected people.

Background: Increased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH). Evidence in animal models have shown that markers of intestinal permeability and microbial translocation vary over the course of the day and are affected by food intake and circadian rhythms. However, daily variations of these markers are not characterized yet in PLWH.