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

The rhythmic circadian repressor REV-ERBα is essential for linking the pulmonary clock to innate immunity.

• Airway epithelial cells act as key circadian pacemakers that regulate inflammatory responses in the lungs.
• Both myeloid and bronchial epithelial cells are involved in the timing and intensity of immune responses to inhaled endotoxin.
• Mutations in REV-ERBα and its paralog REV-ERBβ in bronchial epithelial cells lead to increased inflammatory reactions and a constant state of inflammation.
• REV-ERBα plays a more significant role than REV-ERBβ in regulating inflammatory responses, as loss of REV-ERBβ alone does not affect inflammation.
• Inflammatory stimuli cause significant alterations in the stability and breakdown of REV-ERBα, influenced by specific molecular modifications.
• A new oxazole-based inverse agonist has been developed to prevent the degradation of REV-ERBα, revealing its role in the inflammatory response.

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