Circadian clock gene Period2 regulates a time-of-day-dependent variation in cutaneous anaphylactic reaction.

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 (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-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).

• Authors: Yuki Nakamura, Daisuke Harama, Naomi Shimokawa, Mutsuko Hara, Ryuyo Suzuki, Yu Tahara, Kayoko Ishimaru, Ryohei Katoh, Ko Okumura, Hideoki Ogawa, Shigenobu Shibata, Atsuhito Nakao
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 127 Issue 4 Pg. 1038-45.e1-3 (Apr 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21458659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Per2 protein, mouse
• Period Circadian Proteins
• Immunoglobulin E
• Corticosterone

Topics

• Anaphylaxis (genetics, immunology)
• Animals
• Cell Separation
• Circadian Rhythm (genetics, immunology)
• Corticosterone (blood)
• Flow Cytometry
• Immunoglobulin E (blood)
• Mice
• Mice, Inbred ICR
• Mice, Mutant Strains
• Period Circadian Proteins (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Skin (immunology)