Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris

Br J Dermatol. 2016 Jan;174(1):136-45. doi: 10.1111/bjd.14034. Epub 2015 Nov 11.

Abstract

Background: Psoriasis vulgaris is an inflammatory immune-mediated disease, with lesional skin characterized by sharply demarcated, erythematous scaly plaques. Uninvolved psoriatic skin appears clinically similar to normal skin. However, it has been hypothesized that inflammatory cytokines, e.g. interleukin (IL)-17, may affect any organ or tissue having a vascular supply; thus, distant uninvolved skin could be exposed to increased circulating IL-17.

Objectives: To establish comparative genomic profiles between noninvolved skin and normal skin, in particular, determining immune abnormalities in distant uninvolved skin.

Methods: We performed a meta-analysis on three gene array studies, comparing the nonlesional (NL) psoriatic skin transcriptome with normal gene expression. We investigated immunological features of noninvolved skin, particularly linked to IL-17 signalling.

Results: We detected 252 differentially expressed gene transcripts in uninvolved skin compared with normal skin; multiple immune-related genes, including IL-17-downstream genes, were upregulated. Increased expression of IL-17-signature genes (e.g. DEFB4 and S100A7) was associated with an increased number of CD3+, CD8+ and DC-LAMP+ cells in NL skin vs. normal controls. Inducible T-cell costimulator (ICOS) expression was detected only in a few T-cells within NL skin.

Conclusions: Our data described the genomic profile in NL skin, characterizing the immune activation that was mainly attributed to IL-17 signalling.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-2 / metabolism
  • Lipocalin-2 / genetics
  • Psoriasis / genetics*
  • Psoriasis / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • S100 Calcium Binding Protein A7
  • S100 Proteins / genetics
  • Signal Transduction / physiology
  • beta-Defensins / genetics

Substances

  • DEFB4A protein, human
  • Interleukin-17
  • Interleukin-2
  • LCN2 protein, human
  • Lipocalin-2
  • S100 Calcium Binding Protein A7
  • S100 Proteins
  • S100A7 protein, human
  • beta-Defensins
  • Interferon-gamma