| First Author | Ando N | Year | 2015 |
| Journal | J Invest Dermatol | Volume | 135 |
| Issue | 12 | Pages | 3001-3008 |
| PubMed ID | 26291684 | Mgi Jnum | J:227724 |
| Mgi Id | MGI:5702531 | Doi | 10.1038/jid.2015.316 |
| Citation | Ando N, et al. (2015) Circadian Gene Clock Regulates Psoriasis-Like Skin Inflammation in Mice. J Invest Dermatol 135(12):3001-8 |
| abstractText | 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 gamma/delta(+) T cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R in gamma/delta(+) 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 gamma/delta(+) T cells, establishing a mechanistic link between psoriasis and the circadian clock. |
