title: Transcriptome analysis reveals markers of aberrantly activated innate immunity in vitiligo lesional and non-lesional skin.
abstract: BACKGROUND
  Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients.
  
  
  METHODS
  Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy.
  
  
  RESULTS
  Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients.
  
  
  CONCLUSIONS
  As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting the entire skin surface may improve treatment outcomes. Finally, this study revealed novel mediators that may facilitate future development of vitiligo therapies.
authors.affiliation: Institute of Dermatology, Anhui Medical University, Hefei, China.
authors.forename: Richard
authors.initials: R
authors.lastname: Yu
authors.forename: Raewyn
authors.initials: R
authors.lastname: Broady
authors.forename: Yuanshen
authors.initials: Y
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Megan
authors.initials: M
authors.lastname: Levings
authors.forename: Shencai
authors.initials: S
authors.lastname: Wei
authors.forename: Shengquan
authors.initials: S
authors.lastname: Zhang
authors.forename: Aie
authors.initials: A
authors.lastname: Xu
authors.forename: Mingwan
authors.initials: M
authors.lastname: Su
authors.forename: Jan
authors.initials: J
authors.lastname: Dutz
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008544:Melanocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014820:Vitiligo / Q000235:genetics* / Q000276:immunology / Q000473:pathology