| Literature DB >> 27369778 |
Jun Gui1, Michael Gober2, Xiaoping Yang2, Kanstantsin V Katlinski1, Christine M Marshall2, Meena Sharma2, Victoria P Werth2, Darren P Baker3, Hallgeir Rui4, John T Seykora2, Serge Y Fuchs5.
Abstract
Phototherapy with UV light is a standard treatment for psoriasis, yet the mechanisms underlying the therapeutic effects are not well understood. Studies in human and mouse keratinocytes and in the skin tissues from human patients and mice showed that UV treatment triggers ubiquitination and downregulation of the type I IFN receptor chain IFNAR1, leading to suppression of IFN signaling and an ensuing decrease in the expression of inflammatory cytokines and chemokines. The severity of imiquimod-induced psoriasiform inflammation was greatly exacerbated in skin of mice deficient in IFNAR1 ubiquitination (Ifnar1(SA)). Furthermore, these mice did not benefit from UV phototherapy. Pharmacologic induction of IFNAR1 ubiquitination and degradation by an antiprotozoal agent halofuginone also relieved psoriasiform inflammation in wild-type but not in Ifnar1(SA) mice. These data identify downregulation of IFNAR1 by UV as a major mechanism of the UV therapeutic effects against the psoriatic inflammation and provide a proof of principle for future development of agents capable of inducing IFNAR1 ubiquitination and downregulation for the treatment of psoriasis.Entities:
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Year: 2016 PMID： 27369778 PMCID： PMC5035634 DOI： 10.1016/j.jid.2016.06.608
Source DB: PubMed Journal: J Invest Dermatol ISSN： 0022-202X Impact factor: 8.551