Understanding the Role of Cellular Molecular Clocks in Controlling the Innate Immune Response.
The importance of the 24-h daily cycle, termed circadian, on immune function has been highlighted by a number of recent studies. Immune parameters such as the response to bacterial challenge or immune cell trafficking change with time of day and disruption of circadian rhythms has been linked to inflammatory pathologies. We are beginning to uncover that the key proteins that comprise the molecular clock, most notably BMAL1, CLOCK, and REV-ERBα, also control fundamental aspects of the immune response. Given the ubiquitous nature of the molecular clock in controlling many other types of physiologies such as metabolism and cardiovascular function, a more thorough understanding of the daily rhythm of the immune system may provide important insight into aspects of patient care such as vaccinations and how we manage infectious and inflammatory diseases. In this chapter, we describe a series of experiments to look at circadian expression and function in immune cells. The experiments described herein may provide an initial assessment of the role of the molecular clock on an immune response from any cell type of interest.