Abstract

BackgroundVitiligo 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 and MaterialsPaired 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.ResultsCompared 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 and Clinical ImplicationsAs 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.

Highlights

  • Affecting 0.5%–1% of population worldwide, vitiligo is an acquired pigmentation disorder in which melanocytes are destroyed, resulting in development of porcelain-white patches of skin [1,2,3]

  • The markers of heightened innate immune responses were found to be up-regulated in the non-lesional skin of vitiligo patients

  • Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting the entire skin surface may improve treatment outcomes

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Summary

Introduction

Affecting 0.5%–1% of population worldwide, vitiligo is an acquired pigmentation disorder in which melanocytes are destroyed, resulting in development of porcelain-white patches of skin [1,2,3]. The autoimmune hypothesis stems from the frequently observed association with other autoimmune diseases, such as hypothyroidism and diabetes [19,20,21,22,23] This is further supported by the observation of T-lymphocyte infiltration in human vitiligo lesions and in mouse models [24] and the demonstration of melanocytespecific antibodies in the blood of vitiligo patients. While these results suggest a role for the adaptive immune responses in melanocyte death [25,26,27], there are early suggestions that innate, or natural, immunity in vitiligo is abnormal, as suggested by Jin et al [6], who demonstrated an association between vitiligo susceptibility and genetic changes in a critical innate immunity regulator gene, the NOD-like receptor 1 (NALP1), which has recently been confirmed by immunohistochemistry [28]. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients

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