Altered E-cadherin levels and distribution in melanocytes precede clinical manifestations of vitiligo

Roselyne Y. Wagner, Flavie Luciani, Muriel Cario-André, Alain Rubod, Valérie Petit, Laila Benzekri, Khaled Ezzedine, Sébastien Lepreux, Eirikur Steingrimsson, A. Taieb, Yvon Gauthier, Lionel Larue*, Véronique Delmas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.

Original languageEnglish
Pages (from-to)1810-1819
Number of pages10
JournalJournal of Investigative Dermatology
Volume135
Issue number7
DOIs
Publication statusPublished - 18 Jul 2015

Bibliographical note

Publisher Copyright:
© 2015 The Society for Investigative Dermatology.

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