Department of Immunology, University of Yamanashi Faculty of Medicine, Yamanashi, Japan.
J Allergy Clin Immunol. 2011 Apr;127(4):1038-45.e1-3. doi: 10.1016/j.jaci.2011.02.006.
IgE-mediated immediate-type skin reaction shows a diurnal rhythm, although the precise mechanisms remain uncertain. Period2 (Per2) is a key circadian gene that is essential for endogenous clockworks in mammals.
This study investigated whether Per2 regulates a time-of-day-dependent variation in IgE-mediated immediate-type skin reaction.
The kinetics of a passive cutaneous anaphylactic reaction were compared between wild-type mice and mice with a loss-of-function mutation of Per2 (mPer2(m/m) mice). The effects of adrenalectomy, aging, and dexamethasone on the kinetics of a passive cutaneous anaphylactic reaction were also examined. In addition, the extent of IgE-mediated degranulation in bone marrow-derived mast cells (BMMCs) was compared between wild-type and mPer2(m/m) mice.
A time-of-day-dependent variation in a passive cutaneous anaphylactic reaction observed in wild-type mice was absent in mPer2(m/m) mice and in adrenalectomized and aged mice associated with the loss of rhythmic secretion of corticosterone. In addition, mPer2(m/m) mice showed decreased sensitivity to the inhibitory effects of dexamethasone on the passive cutaneous anaphylactic reactions. IgE-mediated degranulation in BMMCs was comparable between wild-type and mPer2(m/m) mice, but Per2 mutation decreased sensitivity to the inhibitory effects of dexamethasone on IgE-mediated degranulation in BMMCs.
A circadian oscillator, Per2, regulates a time-of-day-dependent variation in a passive cutaneous anaphylactic reaction in mice. Per2 may do so by controlling the rhythmic secretion of glucocorticoid from adrenal glands and/or by gating the glucocorticoid responses of mast cells to certain times of the day (possibly when Per2 levels are high in mast cells).
IgE 介导的即刻型皮肤反应呈昼夜节律，但其确切机制尚不清楚。Period2（Per2）是一种关键的生物钟基因，对哺乳动物内源性时钟机制至关重要。
本研究旨在探讨 Per2 是否调节 IgE 介导的即刻型皮肤反应的时间依赖性变化。
比较野生型小鼠和 Per2 功能丧失突变（mPer2(m/m) 小鼠）小鼠的被动皮肤过敏反应动力学。还研究了肾上腺切除术、衰老和地塞米松对被动皮肤过敏反应动力学的影响。此外，比较了野生型和 mPer2(m/m) 小鼠骨髓来源肥大细胞（BMMC）中 IgE 介导的脱颗粒程度。
野生型小鼠中观察到的被动皮肤过敏反应存在时间依赖性变化，在 mPer2(m/m) 小鼠以及肾上腺切除和衰老小鼠中消失，这与皮质酮节律性分泌的丧失有关。此外，mPer2(m/m) 小鼠对地塞米松抑制被动皮肤过敏反应的作用敏感性降低。BMMC 中 IgE 介导的脱颗粒在野生型和 mPer2(m/m) 小鼠之间相当，但 Per2 突变降低了 BMMC 中 IgE 介导的脱颗粒对地塞米松抑制作用的敏感性。
昼夜节律振荡器 Per2 调节小鼠被动皮肤过敏反应的时间依赖性变化。Per2 可能通过控制肾上腺糖皮质激素的节律性分泌来实现这一点，或者通过调节肥大细胞对一天中某些时间（可能是当肥大细胞中 Per2 水平较高时）的糖皮质激素反应来实现这一点。
