What question did this study set out to answer?

To determine the molecular mechanism by which the circadian repressor REV-ERBα couples the pulmonary clock to innate immunity and regulates lung inflammation.

March 20, 2018Journal of Clinical InvestigationOpen Access

Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation

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To determine the molecular mechanism by which the circadian repressor REV-ERBα couples the pulmonary clock to innate immunity and regulates lung inflammation.
Engineered mouse models with single or dual deletions of REV-ERBα and REV-ERBβ in bronchial epithelial and myeloid cells.
Assessed inflammatory and chemokine responses following inhaled endotoxin challenge across circadian cycles.
Investigated REV-ERBα protein degradation mechanisms involving SUMOylation and ubiquitination, and tested a novel oxazole-based inverse agonist to stabilize the protein.
Deletion of REV-ERBα altered the temporal gating and substantially heightened the amplitude of pulmonary inflammatory responses to inhaled endotoxin, whereas REV-ERBβ deficiency alone caused no effect.
Dual deletion of REV-ERBα and REV-ERBβ in bronchial epithelia triggered a baseline inflammatory state and enhanced chemokine activation in unchallenged cells.
Inflammatory stimulation triggered rapid degradation of REV-ERBα via post-translational SUMOylation and ubiquitination, which was effectively inhibited by the novel oxazole-based inverse agonist.

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Implication

Experimental study reveals that REV-ERBα gates innate immune responses and suppresses basal lung inflammation in mice, highlighting a circadian mechanism regulating respiratory defense.

Cite This Study

Pariollaud et al. (2018) studied this question.

synapsesocial.com/papers/696d7365fa2b4be5f0d96693 https://doi.org/10.1172/jci93910

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Implication

Experimental study reveals that REV-ERBα gates innate immune responses and suppresses basal lung inflammation in mice, highlighting a circadian mechanism regulating respiratory defense.

Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation

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Discussion

Implication

Cite This Study

Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation

Key Points

Discussion

Implication

Cite This Study

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