Role of the biological clock in the physiology of human and mouse mast cells and eosinophils

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Mammals have developed an endogenous circadian clock. Allergic diseases are frequently exacerbated between midnight and early morning, suggesting the involvement of circadian mechanisms. Furthermore, allergy medications, such as glucocorticoids, reset the expression of clock genes in vivo. Interestingly, mast cells and eosinophils, the major inflammatory effector cells in allergy, express specific molecules in a circadian manner. Therefore, we hypothesized that the biological clock might control some functions of mast cells and eosinophils that could be of relevance in allergic disorders. In the present proposal we want to address this hypothesis by 1) investigating the circadian expression of clock genes and proteins and cell-specific molecules in mast cells and eosinophils, 2) determining the need of the circadian clock for eosinophil and mast cell physiology, and 3) analyzing the effects of allergy on circadian expression of clock genes and eosinophil-specific molecules in allergic individuals. Our studies could provide a basis for developing innovative new therapeutic interventions in allergic disease.