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

哺乳动物已经形成了内源性的生物钟。过敏性疾病经常在午夜和清晨之间加重，这表明昼夜节律机制的参与。此外，过敏药物，如糖皮质激素，重置生物钟基因在体内的表达。有趣的是，肥大细胞和嗜酸性粒细胞，过敏反应中的主要炎症效应细胞，以昼夜节律的方式表达特定的分子。因此，我们假设生物钟可能控制肥大细胞和嗜酸性粒细胞的某些功能，这些功能可能与过敏性疾病有关。在本提案中，我们希望通过以下方式来解决这一假设：1）研究肥大细胞和嗜酸性粒细胞中时钟基因和蛋白质以及细胞特异性分子的昼夜节律表达，2）确定嗜酸性粒细胞和肥大细胞生理学对昼夜节律钟的需求，以及3）分析过敏对过敏个体中时钟基因和嗜酸性粒细胞特异性分子的昼夜节律表达的影响。我们的研究可以为开发创新的过敏性疾病新的治疗干预措施提供基础。

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.