Molecular and cellular basis of depigmentation in vitiligo patients

Vitiligo is a chronic skin disease characterized by the appearance of zones of depigmentation. It is mostly described as an autoimmune disease in which the immune system destroys the melanocytes. Consistent with this origin, genetic studies have implicated genes encoding proteins mediating the immune response targeting melanocytes in the aetiology of this disease, together with proteins specific to these cells. However, the destruction of melanocytes by the immune system is neither global nor complete, because the patients do not display total depigmentation. The etiopathology of vitiligo is clearly complex and cannot be simply reduced to an autoimmune reaction directed against pigmented cells. Intrinsic changes have been observed in the melanocytes, keratinocytes and dermal cells of vitiligo patients. Identification of the molecular and cellular changes occurring in normally pigmented skin in vitiligo patients, and an understanding of these changes, is essential to improve the definition of trigger events for this disease, with a view to developing treatments with long‐term efficacy. This review focuses on the early events identified to date in the non‐lesional regions of the skin in vitiligo patients and discusses the process of repigmentation from melanocyte stem cells.

[1]  Z. Aktary,et al.  Epidermal melanocytes in segmental vitiligo show altered expression of E‐cadherin, but not P‐cadherin , 2018, British Journal of Dermatology.

[2]  M. Picardo,et al.  Vitiligo Skin: Exploring the Dermal Compartment. , 2017, The Journal of investigative dermatology.

[3]  N. Hayward,et al.  UVB represses melanocyte cell migration and acts through β‐catenin , 2017, Experimental dermatology.

[4]  M. Picardo,et al.  Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal/Dermal Cross-Talk , 2016, Annals of dermatology.

[5]  R. Ballotti,et al.  Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients. , 2015, The Journal of investigative dermatology.

[6]  D. Roop,et al.  Narrow Band Ultraviolet B Treatment for Human Vitiligo Is Associated with Proliferation, Migration, and Differentiation of Melanocyte Precursors. , 2015, The Journal of investigative dermatology.

[7]  E. Steingrímsson,et al.  Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo. , 2015, The Journal of investigative dermatology.

[8]  H. Nakauchi,et al.  A melanocyte–melanoma precursor niche in sweat glands of volar skin , 2014, Pigment cell & melanoma research.

[9]  A. Abdou,et al.  Immunohistochemical Study of Melanocyte–Melanocyte Stem Cell lineage in Vitiligo; A Clue to Interfollicular Melanocyte Stem Cell Reservoir , 2014, Ultrastructural pathology.

[10]  Piul S. Rabbani,et al.  Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling , 2013, Nature Medicine.

[11]  F. Rambow,et al.  Beta-catenin inhibits melanocyte migration but induces melanoma metastasis , 2013, Oncogene.

[12]  A. Xu,et al.  Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin , 2012, PloS one.

[13]  Young Woo Kim,et al.  E-cadherin inhibits nuclear accumulation of Nrf2: implications for chemoresistance of cancer cells , 2012, Journal of Cell Science.

[14]  Piul S. Rabbani,et al.  Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration , 2011, Cell.

[15]  Emi K Nishimura,et al.  Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation , 2011, Pigment cell & melanoma research.

[16]  T. Hirobe How are proliferation and differentiation of melanocytes regulated? , 2011, Pigment cell & melanoma research.

[17]  H. Nakauchi,et al.  Hair follicle stem cells provide a functional niche for melanocyte stem cells. , 2011, Cell stem cell.

[18]  S. Glassman Vitiligo, reactive oxygen species and T-cells. , 2011, Clinical science.

[19]  N. LaRusso,et al.  Epidermal Growth Factor Protects the Apical Junctional Complexes from Hydrogen peroxide in Bile Duct Epithelium , 2010, Laboratory Investigation.

[20]  Vivek T. Natarajan,et al.  Transcriptional upregulation of Nrf2-dependent phase II detoxification genes in the involved epidermis of vitiligo vulgaris. , 2010, The Journal of investigative dermatology.

[21]  M. Picardo,et al.  Membrane lipid defects are responsible for the generation of reactive oxygen species in peripheral blood mononuclear cells from vitiligo patients , 2010, Journal of cellular physiology.

[22]  M. Herlyn,et al.  Human dermal stem cells differentiate into functional epidermal melanocytes , 2010, Journal of Cell Science.

[23]  G. Girolomoni,et al.  The Role of Innate Immunity in Vitiligo , 2010 .

[24]  M. Waterfield,et al.  Major Role of Epidermal Growth Factor Receptor and Src Kinases in Promoting Oxidative Stress-dependent Loss of Adhesion and Apoptosis in Epithelial Cells* , 2009, The Journal of Biological Chemistry.

[25]  H. Attia,et al.  Antioxidant enzymes and lipid peroxidation at the tissue level in patients with stable and active vitiligo , 2009, International journal of dermatology.

[26]  F. Luciani,et al.  Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. , 2007, Genes & development.

[27]  Elaine Fuchs,et al.  Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. , 2005, Genes & development.

[28]  E Panzig,et al.  In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. , 1999, The journal of investigative dermatology. Symposium proceedings.

[29]  S. Passi,et al.  Increased sensitivity to peroxidative agents as a possible pathogenic factor of melanocyte damage in vitiligo. , 1997, The Journal of investigative dermatology.

[30]  R Kemler,et al.  A role for cadherins in tissue formation. , 1996, Development.

[31]  L. Larue,et al.  E-cadherin null mutant embryos fail to form a trophectoderm epithelium. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Takeichi,et al.  Cadherin cell adhesion receptors as a morphogenetic regulator. , 1991, Science.