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 language | English |
|---|---|
| Pages (from-to) | 3001-3008 |
| Number of pages | 8 |
| Journal | Journal of Investigative Dermatology |
| Volume | 135 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2015 Dec 1 |
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ASJC Scopus subject areas
- Dermatology
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Circadian gene clock regulates psoriasis-like skin inflammation in mice. / Ando, Noriko; Nakamura, Yuki; Aoki, Rui; Ishimaru, Kayoko; Ogawa, Hideoki; Okumura, Ko; Shibata, Shigenobu; Shimada, Shinji; Nakao, Atsuhito.
In: Journal of Investigative Dermatology, Vol. 135, No. 12, 01.12.2015, p. 3001-3008.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Circadian gene clock regulates psoriasis-like skin inflammation in mice
AU - Ando, Noriko
AU - Nakamura, Yuki
AU - Aoki, Rui
AU - Ishimaru, Kayoko
AU - Ogawa, Hideoki
AU - Okumura, Ko
AU - Shibata, Shigenobu
AU - Shimada, Shinji
AU - Nakao, Atsuhito
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84948710442&partnerID=8YFLogxK
U2 - 10.1038/jid.2015.316
DO - 10.1038/jid.2015.316
M3 - Article
C2 - 26291684
AN - SCOPUS:84948710442
VL - 135
SP - 3001
EP - 3008
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 12
ER -