Clockwork Allergy: how circadian clock underpins allergic reaction

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  • Nakao Atsuhito
    Department of Immunology, Faculty of Medicine, University of Yamanashi

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  • アレルギーと概日時計

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Abstract

<p>Symptoms and laboratory parameters of allergic diseases exhibit prominent~24-hour (i.e., circadian) variations. However, the biological basis of this phenomenon remains poorly understood. We have shown that IgE-mediated degranulation in mast cells (i.e., type I allergic reaction) exhibits a time-of-day-dependent variation, which relies on the activity of the internal time-keeping system called "circadian clock". In this case, the clock gene Period2, the expression of which exhibits a~24-hour oscillation, negatively regulates expression of the high-affinity IgE receptor (FcεRI) in mast cell, thereby contributing to the day-night variation in IgE-mediated degranulation. This may explain how allergic disease shows marked day-night changes in the symptoms and laboratory parameters. Importantly, disruption of clock activity not only influences temporal variation, but can also enhance the severity of type I allergic reaction, suggesting that the circadian clock plays more than a simple circadian timekeeping role in allergy. Thus, a better understanding of these processes will provide new insight into previously unknown aspects of the biology of allergies and give us an opportunity to consider how modern lifestyles in the developed world is changing the clinical manifestations of allergy, because sleeping, working, and eating habits are out of sync with endogenous circadian rhythmicity in modern society.</p>

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