Regulation of immune responses by the airway epithelial cell landscape

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(6), P. 347 - 362

Published: Jan. 13, 2021

Language: Английский

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Circadian clock protein Rev-erbα regulates neuroinflammation

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(11), P. 5102 - 5107

Published: Feb. 21, 2019

Circadian dysfunction is a common attribute of many neurodegenerative diseases, most which are associated with neuroinflammation. rhythm has been inflammation in the periphery, but role core clock neuroinflammation remains poorly understood. Here we demonstrate that Rev-erbα, nuclear receptor and circadian component, mediator microglial activation We observed time-of-day oscillation immunoreactivity hippocampus, was disrupted Rev-erbα −/− mice. deletion caused spontaneous hippocampus increased expression proinflammatory transcripts, as well secondary astrogliosis. Transcriptomic analysis from mice revealed predominant inflammatory phenotype suggested dysregulated NF-κB signaling. Primary microglia exhibited phenotypes basal activation. Chromatin immunoprecipitation physically interacts promoter regions several NF-κB–related genes primary microglia. Loss astrocytes had no effect on did potentiate response to lipopolysaccharide (LPS). In vivo, enhanced hippocampal neuroinflammatory responses peripheral LPS injection, while pharmacologic Rev-erbs small molecule agonist SR9009 suppressed LPS-induced influenced neuronal health, conditioned media Rev-erbα–deficient glial cultures exacerbated oxidative damage cultured neurons. also significantly altered cortical resting-state functional connectivity, similar models. Our results reveal pharmacologically accessible link between

Language: Английский

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Perfect timing: circadian rhythms, sleep, and immunity — an NIH workshop summary

JCI Insight, Journal Year: 2020, Volume and Issue: 5(1)

Published: Jan. 15, 2020

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate adaptive responses — ranging from leukocyte mobilization, trafficking, chemotaxis to cytokine release T cell differentiation —are mediated time of day–dependent manner. The National Institutes Health (NIH) recently sponsored an interdisciplinary workshop, “Sleep Insufficiency, Circadian Misalignment, the Immune Response,” highlight new research linking biology function identify areas high translational potential. This Review summarizes topics discussed highlights immediate opportunities delineating clinically relevant connections among biological rhythms, sleep, regulation.

Language: Английский

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Nuclear receptor crosstalk — defining the mechanisms for therapeutic innovation

Nature Reviews Endocrinology, Journal Year: 2020, Volume and Issue: 16(7), P. 363 - 377

Published: April 17, 2020

Language: Английский

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The circadian immune system

Science Immunology, Journal Year: 2022, Volume and Issue: 7(72)

Published: June 3, 2022

The immune system is highly time-of-day dependent. Pioneering studies in the 1960s were first to identify responses be under a circadian control. Only last decade, however, have molecular factors governing rhythms been identified. These revealed complex picture of interconnectivity rhythmicity within cells with that their environment. Here, we provide global overview system, focusing on recent advances rapidly expanding field immunology.

Language: Английский

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Circadian rhythm regulates the function of immune cells and participates in the development of tumors

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 27, 2024

Abstract Circadian rhythms are present in almost all cells and play a crucial role regulating various biological processes. Maintaining stable circadian rhythm is essential for overall health. Disruption of this can alter the expression clock genes cancer-related genes, affect many metabolic pathways factors, thereby affecting function immune system contributing to occurrence progression tumors. This paper aims elucidate regulatory effects BMAL1, other on cells, reveal molecular mechanism rhythm’s involvement tumor its microenvironment regulation. A deeper understanding has potential provide new strategies treatment cancer immune-related diseases.

Language: Английский

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Basic helix–loop–helix ARNT like 1 regulates the function of immune cells and participates in the development of immune-related diseases

Burns & Trauma, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

The circadian clock is an internal timekeeper system that regulates biological processes through a central and peripheral clocks controlling various genes. Basic helix-loop-helix ARNT-like 1 (BMAL1), also known as aryl hydrocarbon receptor nuclear translocator-like protein (ARNTL1), key component of the clock. deletion BMAL1 alone can abolish rhythms human body. plays critical role in immune cell function. Dysregulation linked to immune-related diseases such autoimmune diseases, infectious cancer, vice versa. This review highlights significant governing cells, including their development, differentiation, migration, homing, metabolism, effector functions. study explores how dysregulation have far-reaching implications potentially contribute onset sepsis, trauma. Furthermore, this discusses treatments for target disorders. Understanding impact on function provide insights into pathogenesis help development more effective treatment strategies. Targeting has been demonstrated achieve good efficacy indicating its promising potential targetable therapeutic these diseases.

Language: Английский

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Molecular Interactions Between Components of the Circadian Clock and the Immune System

Journal of Molecular Biology, Journal Year: 2020, Volume and Issue: 432(12), P. 3700 - 3713

Published: Jan. 10, 2020

The immune system is under control of the circadian clock. Many rhythms observed in originate direct interactions between components clock and system. main means over by proteins acting as transcription factors driving expression or repression genes. A second immunity lies acetylation methylation histones to regulate gene inflammatory proteins. Furthermore, can engage physical with key pathways such members NFκB protein family. This regulation independent allows also reciprocally exert function. Thus, molecular are manifold. We highlight discuss here recent findings respect mechanisms that time-of-day-dependent immunity. review provides a structured overview focusing on discusses their reciprocal

Language: Английский

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Circadian control of lung inflammation in influenza infection

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 11, 2019

Influenza is a leading cause of respiratory mortality and morbidity. While inflammation essential for fighting infection, balance anti-viral defense host tolerance necessary recovery. Circadian rhythms have been shown to modulate inflammation. However, the importance diurnal variability in timing influenza infection not well understood. Here we demonstrate that endogenous affect survival infection. control mediated by enhanced as proven increased cellularity bronchoalveolar lavage (BAL), pulmonary transcriptomic profile histology attributable viral burden. Better associated with time dependent preponderance NK NKT cells lower proportion inflammatory monocytes lung. Further, using series genetic mouse mutants, elucidate cellular mechanisms underlying circadian gating

Language: Английский

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Inhibition of REV‐ERBs stimulates microglial amyloid‐beta clearance and reduces amyloid plaque deposition in the 5XFAD mouse model of Alzheimer’s disease

Aging Cell, Journal Year: 2019, Volume and Issue: 19(2)

Published: Dec. 4, 2019

A promising new therapeutic target for the treatment of Alzheimer's disease (AD) is circadian system. Although patients with AD are known to have abnormal rhythms and suffer sleep disturbances, role molecular clock in regulating amyloid-beta (Aβ) pathology still poorly understood. Here, we explored how repressors REV-ERBα β affected Aβ clearance mouse microglia. We discovered that, at Circadian time 4 (CT4), microglia expressed higher levels master protein BMAL1 more rapidly phagocytosed fibrillary Aβ1-42 (fAβ1-42 ) than CT12. directly drives transcription REV-ERB proteins, which implicated microglial activation. Interestingly, pharmacological inhibition REV-ERBs small molecule antagonist SR8278 or genetic knockdown REV-ERBs-accelerated uptake fAβ1-42 increased BMAL1. also promoted polarization toward a phagocytic M2-like phenotype P2Y12 receptor expression. Finally, constitutive deletion Rev-erbα 5XFAD model decreased amyloid plaque number size prevented plaque-associated increases disease-associated markers including TREM2, CD45, Clec7a. Altogether, our work suggests novel strategy controlling neuroinflammation by targeting provides insights into AD.

Language: Английский

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