Clock Proteins and Circadian Rhythms in Immunity

Abstract

The circadian clock influences many, if not all, aspects of immunity. Variations across daily time scales have been observed in immune cell migration, differentiation and effector function, including cytokine/chemokine production, phagocytosis, antigen presentation, lymphocyte proliferation and the allergic response. Circadian clock disruption caused by environmental or genetic means often results in immune system dysfunction. These circadian influences on immunity are mediated through systemic autonomic and hormonal variations, in coordination with intrinsic clocks residing in immune cells and structural cells of the microenvironment. Several inflammatory conditions such as bronchial asthma and rheumatoid arthritis show circadian variations in symptomatology. Other inflammatory conditions, such as cardiovascular disease and responses to organ and cell transplantation also display daily rhythmicity and enhanced severity with circadian disruption. In this chapter, we will address the many types of circadian rhythms present in immunity, shedding light on the underlying molecular mechanisms that operate within cells of the innate and adaptive immune system. We will address how circadian molecular changes within immune cells are linked with immune cell fate and function. Finally, we will briefly discuss the impact of the immune clock on human health and disease and discuss how we can harness the inherent rhythmicity in our immune system to modify pharmacological responses.