Circadian Gene Clock Regulates Psoriasis-Like Skin Inflammation in Mice

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860874
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: University of Yamanashi
• Principal Investigator: ANDO Noriko 山梨大学, 総合研究部, 助教 (90345710)
• Research Collaborator: NAKAO Atsuhito 山梨大学, 総合研究部, 教授 (80317445) ; NAKAMURA Yuki 山梨大学, 総合研究部, 講師 (90580465) ; SHIMADA Shinji 山梨大学, 総合研究部, 教授 (10114505)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: circadian / clock / IL23R / psoriasis / imiquimod

Outline of Final Research Achievements

The mechanistic link between psoriasis and "the circadian clock," remains unclear. This study determined whether the core circadian gene, Clock, had a regulatory role in the development of psoriasis. We compared the development of psoriasis-like skin inflammation induced by imiquimod (IMQ) between wild-type mice and mice with a loss-of-function mutation of Clock. We also compared the development of dermatitis between wild-type mice and mice with a loss-of-function mutation of Period2 (Per2), another key circadian gene that inhibits CLOCK activity. We found that Clock mutation ameliorated IMQ-induced dermatitis, whereas the Per2 mutation exaggerated IMQ-induced dermatitis, when compared with wild-type mice associated with decreased or increased IL-23 receptor (IL-23R) expression in γ/δ+ T cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R in γ/δ+ T cells. These findings established a mechanistic link between psoriasis and the circadian clock.

Free Research Field

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