title: Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratory of Investigative Dermatology, The Rockefeller University, New York City, NY, U.S.A.|Department of Dermatology, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chiricozzi
authors.affiliation: Center for Clinical and Translational Science, The Rockefeller University, New York City, NY, U.S.A.
authors.forename: M
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory of Investigative Dermatology, The Rockefeller University, New York City, NY, U.S.A.
authors.forename: J
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.affiliation: Laboratory of Investigative Dermatology, The Rockefeller University, New York City, NY, U.S.A.
authors.forename: I
authors.initials: I
authors.lastname: Cueto
authors.affiliation: Immunology Systems Pharmacology & Biomarkers, Janssen Research & Development, Radnor, PA, U.S.A.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.affiliation: Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: S
authors.initials: S
authors.lastname: Tian
authors.affiliation: Immunology Systems Pharmacology & Biomarkers, Janssen Research & Development, Radnor, PA, U.S.A.
authors.forename: C
authors.initials: C
authors.lastname: Brodmerkel
authors.affiliation: Laboratory of Investigative Dermatology, The Rockefeller University, New York City, NY, U.S.A.
authors.forename: J G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D000071068:Lipocalin-2 / Q000235:genetics; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D023083:beta-Defensins / Q000235:genetics
chemical_list: C106641:DEFB4A protein, human; D020381:Interleukin-17; D007376:Interleukin-2; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D023083:beta-Defensins; D007371:Interferon-gamma