Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients

J Invest Dermatol. 2015 Dec;135(12):3105-3114. doi: 10.1038/jid.2015.335. Epub 2015 Aug 31.


Vitiligo affects 1% of the worldwide population. Halting disease progression and repigmenting the lesional skin represent the two faces of therapeutic challenge in vitiligo. We performed transcriptome analysis on lesional, perilesional, and non-depigmented skin from vitiligo patients and on matched skin from healthy subjects. We found a significant increase in CXCL10 in non-depigmented and perilesional vitiligo skin compared with levels in healthy control skin; however, neither CXCL10 nor other immune factors were deregulated in depigmented vitiligo skin. Interestingly, the WNT pathway, which is involved in melanocyte differentiation, was altered specifically in vitiligo skin. We demonstrated that oxidative stress decreases WNT expression/activation in keratinocytes and melanocytes. We developed an ex vivo skin model and confirmed the decrease activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated ex vivo depigmented skin from vitiligo patients and successfully induced differentiation of resident stem cells into pre-melanocytes. Our results shed light on the previously unrecognized role of decreased WNT activation in the prevention of melanocyte differentiation in depigmented vitiligo skin. Furthermore, these results support further clinical exploration of WNT agonists to repigment vitiligo lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CXCL10 / analysis
  • Gene Expression Profiling*
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / physiology
  • Oxidative Stress
  • Skin / metabolism*
  • Skin Pigmentation*
  • Vitiligo / etiology
  • Vitiligo / physiopathology*
  • Wnt Signaling Pathway*


  • CXCL10 protein, human
  • Chemokine CXCL10
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1