Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 136, Issue 10, Pages 1990-2002Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2016.06.608
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Funding
- NCI NIH HHS [P01 CA165997, R01 CA188575, T32 CA009140, R01 CA092900] Funding Source: Medline
- NIAMS NIH HHS [T32 AR007465] Funding Source: Medline
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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.
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