Type I interferon signature in the initiation of the immune response in vitiligo

Pigment Cell Melanoma Res. 2014 May;27(3):398-407. doi: 10.1111/pcmr.12219. Epub 2014 Feb 21.

Abstract

Immune-mediated responses are consistently observed in progressing vitiligo at the edge of depigmenting patches. Besides the role of the adaptive immune system, the profile of the innate immune response is now at the center of the stage. We report that plasmacytoid dendritic cells (pDC), which are the major interferon (IFN)-alpha-producing cells, are part of the infiltrate of progressive vitiligo with local production of MxA (a protein induced by IFNα). MxA was associated with expression of the type I IFN-inducible ligand CXCL9 and correlated with the recruitment of CXCR3(+) immune cells. Interestingly, strong MxA expression was observed in perilesional skin in close apposition to remaining melanocytes, surrounded by a prominent T-cell infiltrate. In contrast, MxA was not detectable in lesional skin, suggesting that IFN-α production is an early event in the progression of the disease. Our data highlight a new innate immune pathway leading to progression of vitiligo.

Keywords: innate immunity; interferon-alpha; plasmacytoid dendritic cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoimmune Diseases / complications
  • Chemokine CXCL9 / biosynthesis*
  • Chemokine CXCL9 / genetics
  • Chemotaxis, Leukocyte
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Immunity, Innate
  • Inflammation
  • Interferon-alpha / physiology*
  • Male
  • Middle Aged
  • Myxovirus Resistance Proteins / biosynthesis*
  • Myxovirus Resistance Proteins / genetics
  • Nevus, Halo / etiology
  • Receptors, CXCR3 / analysis
  • Skin / metabolism*
  • Skin / pathology
  • T-Lymphocyte Subsets / immunology
  • Transcriptome*
  • Vitiligo / complications
  • Vitiligo / immunology*
  • Vitiligo / metabolism
  • Vitiligo / pathology
  • Young Adult

Substances

  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL9
  • Interferon-alpha
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • Receptors, CXCR3