Circadian regulation of neutrophils: Control by a cell-autonomous clock or systemic factors?

Abstract

Background: The circadian time-measuring system enables the organism to anticipate and effectively respond to regular daily changes in the environment and is therefore a crucial factor of adaptation. A large body of epidemiological data underlines the circadian characteristics of human immune functions. Circadian control of neutrophil responsiveness contributes to daily changes in the pathology of both acute and chronic inflammation and may therefore time-dependently influence the outcome of therapeutic approaches. Aim: This review summarizes recent data on the role of the circadian clock in the control of immune responses, particularly of those linked to neutrophil activity, and possible mechanisms of the regulation. Discussion: In the first section of this review we present the recent model of the mammalian molecular clock by introducing the main transcription-translation feedback loops and discussing the pace-setting role of post-translational modifications. The next sections summarize clinical, epidemiological and experimental data regarding the daily control of immune responses and studies analysing expression of clock components in various leukocytes and particularly, in human peripheral neutrophils. As the latter data indicate that expression of components of the cell-autonomous clock is relatively low in neutrophils, in the last section we review recent findings suggesting a role for systemic and local factors in the regulation of rhythmic neutrophil responses.