書誌： J ALLERGY CLIN IMMUNOL ,2011
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 4, 1038-1045
Yuki Nakamura,Daisuke Harama, Naomi Shimokawa, PhD, Mutsuko Hara, Ryuyo Suzuki, MD, PhD, Yu Tahara, Kayoko Ishimaru, Ryohei Katoh, MD, PhD, Ko Okumura, MD, PhD, Hideoki Ogawa, MD, PhD, Shigenobu Shibata, PhD, and Atsuhito Nakao, MD, PhD
Background: 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. Objective: This study investigated whether Per2 regulates a time-of-day–dependent variation in IgE-mediated immediatetype skin reaction. Methods: 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. Results: 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. Conclusion: A circadian oscillator, Per2, regulates a time-ofday–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). (J Allergy Clin Immunol 2011;127:1038-45.)
Key words: Circadian rhythm, clock, Period2, IgE, mast cell, anaphylactic reaction, mouse