Clock control of inflammation in the lung. (360G-Wellcome-107851_Z_15_Z)
Circadian rhythms dominate virtually all aspects of human physiology. It is now established that disruption of the circadian clock has a profound impact on inflammation in both humans and in animal models. Unexpectedly, clock mediation of inflammatory responses extends not only to the magnitude of response, but also its sensitivity to anti-inflammatory glucocorticoid signals. This proposal focuses on pulmonary inflammation, and capitalises on unique genetic models and pharmacological tools devel oped by our group to address a fundamental question: How does the clock control host defence? Specifically, we will elucidate: 1: How time-keeping and inflammatory cells communicate to shape pulmonary immune response 2: How the molecular clock controls pro- and anti-inflammatory signalling within the lung 3: How clock regulation of epigenetic structure mediates inflammatory set point
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