title: 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.
  
  
  CONCLUSIONS
  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: Department of Immunology, University of Yamanashi Faculty of Medicine, Yamanashi, Japan.
authors: Yuki
authors: Y
authors: Nakamura
authors: Daisuke
authors: D
authors: Harama
authors: Naomi
authors: N
authors: Shimokawa
authors: Mutsuko
authors: M
authors: Hara
authors: Ryuyo
authors: R
authors: Suzuki
authors: Yu
authors: Y
authors: Tahara
authors: Kayoko
authors: K
authors: Ishimaru
authors: Ryohei
authors: R
authors: Katoh
authors: Ko
authors: K
authors: Okumura
authors: Hideoki
authors: H
authors: Ogawa
authors: Shigenobu
authors: S
authors: Shibata
authors: Atsuhito
authors: A
authors: Nakao
mesh_terms: D000707:Anaphylaxis / Q000235:genetics* / Q000276:immunology; D000818:Animals; D002469:Cell Separation; D002940:Circadian Rhythm / Q000235:genetics* / Q000276:immunology*; D003345:Corticosterone / Q000097:blood; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D056950:Period Circadian Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*
chemical_list: C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D007073:Immunoglobulin E; D003345:Corticosterone