Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques

J Invest Dermatol. 2010 Nov;130(11):2654-63. doi: 10.1038/jid.2010.166. Epub 2010 Jun 17.

Abstract

Narrow-band UVB radiation (NB-UVB) therapy offers a well-established treatment modality for psoriasis. However, despite the common use of this form of treatment, the mechanism of action of NB-UVB is not well understood. We studied a group of 14 patients with moderate-to-severe psoriasis treated with carefully titrated and monitored NB-UVB for 6 weeks. Lesional plaques were classified as normalized (n=8) or nonresponsive (n=6) based on their histological improvement and normalization. We characterized lesional myeloid dendritic cells (DCs) and T cells and their inflammatory mediators using immunohistochemistry and real-time PCR. NB-UVB suppressed multiple parameters of the IL-23/IL-17 pathway in normalized plaques, but not in nonresponsive plaques. NB-UVB decreased the numbers of CD11c(+) DCs, specifically CD1c(-)CD11c(+) "inflammatory" DCs, and their products, IL-20, inducible nitric oxide synthase, IL-12/23p40, and IL-23p19. Furthermore, effective NB-UVB suppressed IL-17 and IL-22 mRNAs, which strongly correlated with lesion resolution. Therefore, in addition to its known role in suppressing IFN-γ production, NB-UVB radiation therapy can also target the IL-17 pathway to resolve psoriatic inflammation.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub.

Trial registration: ClinicalTrials.gov NCT00220025.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Gene Expression / immunology
  • Gene Expression / radiation effects
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-23 / genetics
  • Interleukin-23 / immunology*
  • Interleukin-23 / metabolism
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Psoriasis / radiotherapy*
  • Skin / immunology
  • Skin / pathology
  • Skin / radiation effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Ultraviolet Therapy / methods*

Substances

  • Interleukin-17
  • Interleukin-23
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00220025