Date: 2014/8/1

Venue: Lecture room No. 2, School of Agriculture

Time: 16:30 - 18:00

Speaker: Prof. Andrew Loudon
Faculty of Life Sciences, University of Manchester, UK

Title: Circadian clock control of immune function and inflammation

Within cells of the immune system, the circadian clock drives robust rhythmic inflammatory responses in tissues, but clock-disruption commonly leads to an elevated chronic inflammatory state. Although normal inflammatory responses are essential components in the body's defense mechanism, chronic elevated inflammation within tissues underpins multiple disease states. We are therefore interested in defining the circadian mechanisms driving inflammation and cell types and pathways are involved. Using mice, we have targeted a major clock-regulating protein (BMAL1) in macrophage cells, and shown that this disrupts normal rhythmic inflammatory responses to systemic endotoxin. This appears to be mediated via REVERB proteins, which regulate rhythmic expression of pro-inflammatory cytokines. We have recently extended these studies to the lung, and now reveal an important role for pulmonary epithelial cells as local circadian pacemakers, regulating rhythmic chemokine signaling and responses to infection. This action involves glucocorticoids, as clock targeting of lung epithelial cells prevents the glucocorticoid receptor (GR) from binding rhythmically to target chemokine genes, leading to elevated inflammation. This defines a novel regulatory mechanism that links the circadian clock in target tissues to circulating glucocorticoid hormones acting on the GR. These need to operate in resonance to control normal time-of-day variation in the magnitude of pulmonary inflammation and responses to bacterial infection.

In this time, he will give us a lecture titled ''Circadian clock control of immune function and inflammation''.

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