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Circadian clock gene Period2 regulates a time-of-day–dependent variation in cutaneous anaphylactic reaction - 11/08/11

Doi : 10.1016/j.jaci.2011.02.006 
Yuki Nakamura a, Daisuke Harama a, Naomi Shimokawa, PhD a, Mutsuko Hara c, Ryuyo Suzuki, MD, PhD c, Yu Tahara d, Kayoko Ishimaru a, Ryohei Katoh, MD, PhD b, Ko Okumura, MD, PhD c, Hideoki Ogawa, MD, PhD c, Shigenobu Shibata, PhD d, Atsuhito Nakao, MD, PhD a, c,
a Department of Immunology, University of Yamanashi Faculty of Medicine, Yamanashi, Japan 
b Department of Pathology, University of Yamanashi Faculty of Medicine, Yamanashi, Japan 
c Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan 
d Department of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan 

Reprint requests: Atsuhito Nakao, MD, PhD, Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.

Abstract

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 immediate-type 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 (mPer2m/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 mPer2m/m mice.

Results

A time-of-day–dependent variation in a passive cutaneous anaphylactic reaction observed in wild-type mice was absent in mPer2m/m mice and in adrenalectomized and aged mice associated with the loss of rhythmic secretion of corticosterone. In addition, mPer2m/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 mPer2m/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-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).

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Key words : Circadian rhythm, clock, Period2, IgE, mast cell, anaphylactic reaction, mouse

Abbreviations used : BMMC, GAPDH, Per2, Per2::LUC, SCN, ZT


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 Supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
 Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.


© 2011  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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