title: Constant light exposure impairs immune tolerance development in mice.
abstract: BACKGROUND
  An intrinsic daily physiological rhythm called circadian rhythm has been indicated to affect the immune system and its related diseases. Immune tolerance development is closely associated with the onset of immunological disorders. However, the effect of circadian rhythm in the mechanisms of immune tolerance development has not yet been fully understood.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the effects of circadian rhythm disruption on the development of immune tolerance by the perturbation of light environment, using a mouse model of neonatally induced cutaneous tolerance.
  
  
  METHODS
  Mice were kept under constant light (LL) or light-dark (LD) conditions, and hapten was applied at 2days after birth. Six weeks later, hapten was reapplied to abdominal skin, followed by hapten application to ear skin 5days later.
  
  
  RESULTS
  The ear-swelling responses and cell infiltration into inflamed skin significantly increased in LL mice compared with those in LD mice. Interestingly, the percentage and the number of Foxp3+-regulatory T cells notably decreased in inflamed skin and draining lymph nodes of LL mice compared with that in LD mice. Loss-of-function mutation of a key circadian gene, Bmal1, also exacerbated the ear-swelling responses and cell infiltration into inflamed skin in mice.
  
  
  CONCLUSIONS
  These results suggest that circadian rhythm may be implicated in immune tolerance development in allergic inflammation.
authors.affiliation: Departments of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mizutani
authors.affiliation: Departments of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: risat@koto.kpu-m.ac.jp.
authors.forename: Risa
authors.initials: R
authors.lastname: Tamagawa-Mineoka
authors.affiliation: Department of Physiology and Systems Bioscience, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Minami
authors.affiliation: Department of Physiology and Systems Bioscience, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yagita
authors.affiliation: Departments of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: nkatoh@koto.kpu-m.ac.jp.
authors.forename: Norito
authors.initials: N
authors.lastname: Katoh
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics*; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000528:radiation effects*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D055786:Gene Knockout Techniques; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D008027:Light / Q000009:adverse effects*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012867:Skin / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006241:Haptens
keywords: Constant light; Contact hypersensitivity; Neonatal immune tolerance; Regulatory T cell