Circadian clock regulation of mucosal immunity

Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models we now identify the rhythmic circadian repressor REV-ERB as essential to the mechanism coupling the pulmonary clock to innate immunity. Dual mutation of REV-ERBα and its paralog REV-ERBβ in bronchial epithelia further augmented inflammatory responses and chemokine activation, but also initiated a basal inflammatory state, revealing a critical homeostatic role for REV-ERB proteins in the suppression of the endogenous pro-inflammatory mechanism in un-challenged cells. Thus, dynamic changes in stability of REV-ERB protein couple the core clock to innate immunity.
David trained in general internal medicine and endocrinology in the UK, and California. He developed a research interest in nuclear receptor function in inflammation, which was supported by MRC, and GSK fellowships. He then identified the importance of the circadian clock machinery in regulating innate immunity, using lung, joint and gut models, and is extending these studies to human cohorts. He recently moved to Oxford, with Wellcome and MRC support, to work on circadian control of inflammation in the lung, and the re-wiring of circadian metabolism by chronic inflammatory processes.