| Project/Area Number |
26860874
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
ANDO Noriko 山梨大学, 総合研究部, 助教 (90345710)
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| 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)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | circadian / clock / IL23R / psoriasis / imiquimod / IL23receptor / 体内時計 / 乾癬 / IL-23 receptor |
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| 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.
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