Time will tell about mast cells: Circadian control of mast cell activation

Abstract

Mast cell activation is crucial to the development of allergic disease. New studies have shown that both IgE-dependent and -independent mast cell activation is temporally regulated by the circadian clock, a time-of-day-keeping system that consists of transcriptional-translational feedback loops of several clock genes. For instance, the core clock gene Clock controls the expression of the high-affinity IgE receptor (FcεRI) and interleukin-33 (IL-33) receptor ST2 on mast cells in a time-dependent manner. As a result, the threshold of IgE-dependent or IL-33-dependent mast cell activation differs between daytime and nighttime. This mechanism may underlie the observation that allergic disease shows a marked day-night change in symptom occurrence and severity. Consistent with this novel concept, environmental and lifestyle factors that disturb the normal rhythmicity of the circadian clock, such as irregular eating habits, can lead to the loss of circadian control of mast cell activation. Consequently, the degree of mast cell activation becomes equally strong at all times of day, which might clinically result in worsening allergic symptoms. Therefore, further understanding of the association between mast cell activation and the circadian clock is important to better manage patients with allergic disease in the real world, characterized by a “24/7 society” filled with environmental and lifestyle factors that disturb the circadian clock rhythmicity.