Circadian gene clock regulates psoriasis-like skin inflammation in mice

Noriko Ando, Yuki Nakamura, Rui Aoki, Kayoko Ishimaru, Hideoki Ogawa, Ko Okumura, Shigenobu Shibata, Shinji Shimada, Atsuhito Nakao

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    19 Citations (Scopus)

    Abstract

    There are several reports suggesting that the pathophysiology of psoriasis may be associated with aberrant circadian rhythms. However, the mechanistic link between psoriasis and the circadian time-keeping system, "the circadian clock," remains unclear. This study determined whether the core circadian gene, Clock, had a regulatory role in the development of psoriasis. For this purpose, we compared the development of psoriasis-like skin inflammation induced by the Toll-like receptor 7 ligand imiquimod (IMQ) between wild-type mice and mice with a loss-of-function mutation of Clock. We also compared the development of IMQ-induced 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, and IL-23R expression in the mouse skin was under circadian control. These findings suggest that Clock is a novel regulator of psoriasis-like skin inflammation in mice via direct modulation of IL-23R expression in γ/δ + T cells, establishing a mechanistic link between psoriasis and the circadian clock.

    Original languageEnglish
    Pages (from-to)3001-3008
    Number of pages8
    JournalJournal of Investigative Dermatology
    Volume135
    Issue number12
    DOIs
    Publication statusPublished - 2015 Dec 1

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    ASJC Scopus subject areas

    • Dermatology
    • Biochemistry
    • Cell Biology
    • Molecular Biology

    Cite this

    Ando, N., Nakamura, Y., Aoki, R., Ishimaru, K., Ogawa, H., Okumura, K., Shibata, S., Shimada, S., & Nakao, A. (2015). Circadian gene clock regulates psoriasis-like skin inflammation in mice. Journal of Investigative Dermatology, 135(12), 3001-3008. https://doi.org/10.1038/jid.2015.316