Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses

Immunity, Год журнала: 2017, Номер 46(1), С. 120 - 132

Опубликована: Янв. 1, 2017

Lymphocytes circulate through lymph nodes (LN) in search for antigen what is believed to be a continuous process. Here, we show that lymphocyte migration and occurred non-continuous, circadian manner. Lymphocyte homing peaked at night onset, with cells leaving the tissue during day. This resulted strong oscillations cellularity efferent lymphatic fluid. Using lineage-specific genetic ablation of clock function, demonstrated this dependent on rhythmic expression promigratory factors lymphocytes. Dendritic cell numbers phase lymphocytes, diurnal being present disease severity after immunization induce experimental autoimmune encephalomyelitis (EAE). These rhythms were abolished by disruption T clocks, demonstrating regulation time-of-day critical adaptive immune responses weeks later.

Язык: Английский

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Macrophages and Iron Metabolism

Immunity, Год журнала: 2016, Номер 44(3), С. 492 - 504

Опубликована: Март 1, 2016

Язык: Английский

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Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1

Proceedings of the National Academy of Sciences, Год журнала: 2015, Номер 112(23), С. 7231 - 7236

Опубликована: Май 20, 2015

The response to an innate immune challenge is conditioned by the time of day, but molecular basis for this remains unclear. In myeloid cells, there a temporal regulation induction lipopolysaccharide (LPS) proinflammatory microRNA miR-155 that correlates inversely with levels BMAL1. BMAL1 in lineage inhibits activation NF-κB and protects mice from LPS-induced sepsis. Bmal1 has two miR-155-binding sites its 3'-UTR, and, LPS, binds these target sites, leading suppression mRNA protein humans. deletion perturbs circadian function, gives rise shorter ablates effect on cytokine responses LPS. Thus, clock controls can repress directly. This leads variably responsive challenges across day.

Язык: Английский

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Immunity around the clock

Science, Год журнала: 2016, Номер 354(6315), С. 999 - 1003

Опубликована: Ноя. 24, 2016

Immunity is a high-cost, high-benefit trait that defends against pathogens and noxious stimuli but whose overactivation can result in immunopathologies sometimes even death. Because many immune parameters oscillate rhythmically with the time of day, circadian clock has emerged as an important gatekeeper for reducing immunity-associated costs, which, turn, enhances organismal fitness. This mediated by interactions between extrinsic environmental cues intrinsic oscillators cells, which together optimize responses throughout cycle. The elucidation these clock-controlled immunomodulatory mechanisms might uncover new approaches treating infections chronic inflammatory diseases.

Язык: Английский

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Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors

The Journal of Experimental Medicine, Год журнала: 2014, Номер 211(13), С. 2583 - 2598

Опубликована: Ноя. 24, 2014

Lymphocyte recirculation through secondary lymphoid organs is essential for immunosurveillance and lymphocyte effector functions. Here, we show that signals β2-adrenergic receptors (β2ARs) expressed on lymphocytes are involved in the control of dynamics by altering responsiveness chemoattractant receptors. Agonist stimulation β2ARs inhibited egress from lymph nodes (LNs) rapidly produced lymphopenia mice. Physiological inputs adrenergic nerves contributed to retention within LNs homeostasis their distribution among tissues. physically interacted with CCR7 CXCR4, chemokine promoting LNs. Activation enhanced retention-promoting consequently In models T cell–mediated inflammatory diseases, β2AR-mediated LN antigen-primed cells reduced recruitment into peripheral Thus, this study reveals a novel mechanism controlling trafficking provides additional insights immune regulation nervous system.

Язык: Английский

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Microglia inflammatory responses are controlled by an intrinsic circadian clock

Brain Behavior and Immunity, Год журнала: 2014, Номер 45, С. 171 - 179

Опубликована: Ноя. 26, 2014

Язык: Английский

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Circadian timing of metabolism in animal models and humans

Journal of Internal Medicine, Год журнала: 2015, Номер 277(5), С. 513 - 527

Опубликована: Янв. 20, 2015

Most living beings, including humans, must adapt to rhythmically occurring daily changes in their environment that are generated by the Earth's rotation. In course of evolution, these organisms have acquired an internal circadian timing system can anticipate environmental oscillations and thereby govern rhythmic physiology a proactive manner. mammals, coordinates virtually all physiological processes encompassing vigilance states, metabolism, endocrine functions cardiovascular activity. Research performed during past two decades has established almost every cell body possesses its own timekeeper. The resulting clock network is organized hierarchical A master pacemaker, located suprachiasmatic nucleus (SCN) hypothalamus, synchronized day photoperiod. turn, SCN determines phase cellular clocks peripheral organs through wide variety signalling pathways dependent on feeding cycles, temperature rhythms, oscillating bloodborne signals and, some organs, inputs nervous system. major purpose tissues temporal orchestration key metabolic processes, food processing (metabolism xenobiotic detoxification). Here, we review recent findings regarding molecular composition discuss implications for coordination metabolism health disease. We focus primarily disorders such as obesity type 2 diabetes, although misalignments (shiftwork or 'social jet lag') also been associated with aetiology human malignancies.

Язык: Английский

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Circadian Rhythm and the Gut Microbiome

International review of neurobiology, Год журнала: 2016, Номер unknown, С. 193 - 205

Опубликована: Янв. 1, 2016

Язык: Английский

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Cell autonomous regulation of herpes and influenza virus infection by the circadian clock

Proceedings of the National Academy of Sciences, Год журнала: 2016, Номер 113(36), С. 10085 - 10090

Опубликована: Авг. 15, 2016

Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication unknown. We find the time of day infection regulates virus progression live mice individual cells. Furthermore, we demonstrate herpes influenza A infections enhanced when abolished by disrupting key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, chromatin assembly all contribute regulation infection. Moreover, herpesviruses differentially target components molecular clockwork. Our work demonstrates viruses exploit clockwork for their own gain represents a novel modulating extends beyond any single family these ubiquitous pathogens.

Язык: Английский

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Aged neutrophils contribute to the first line of defense in the acute inflammatory response

Blood, Год журнала: 2016, Номер 128(19), С. 2327 - 2337

Опубликована: Сен. 9, 2016

Язык: Английский

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