Therapeutic Elimination of the Type 1 Interferon Receptor for Treating Psoriatic Skin Inflammation. J Invest Dermatol 2016 Oct;136(10):1990-2002
Date
07/03/2016Pubmed ID
27369778Pubmed Central ID
PMC5035634DOI
10.1016/j.jid.2016.06.608Scopus ID
2-s2.0-84996743478 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
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.
Author List
Gui J, Gober M, Yang X, Katlinski KV, Marshall CM, Sharma M, Werth VP, Baker DP, Rui H, Seykora JT, Fuchs SYMESH terms used to index this publication - Major topics in bold
AnimalsCell Line
Chemokines
Cytokines
Disease Models, Animal
Down-Regulation
Humans
Inflammation
Keratinocytes
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Piperidines
Psoriasis
Quinazolinones
Receptor, Interferon alpha-beta
Signal Transduction
Skin
Ubiquitination
Ultraviolet Therapy
