The club cell circadian clock regulates temporal patterns in leukocyte trafficking in chronic allergic airways...

Patients with allergic asthma exhibit distinct temporal variations in symptoms and disease severity, which oscillate across the 24 h day. We have previously shown that the molecular circadian clock plays a critical role in temporally gating the response to allergen challenge in mice. Club cells, a subset of pulmonary bronchial epithelial cells, are implicated in the gating of time-dependent responses to type-1 inflammatory stimuli and trafficking of neutrophils to the lung. Using a club cell specific Bmal1 knockout mouse (CCSP-Bmal1 KO) we found that this is also true in the setting of chronic type-2 pulmonary inflammation, where eosinophil and T-helper 2 cell trafficking patterns were abolished in mice lacking a functional circadian clock within the lung. Notably, we find that circadian patterns in airway permeability are lost in CCSP-Bmal1 KO mice, rendering the barrier equally permissible to trafficking cells at all times of day.