Background:
Vitiligo is an acquired chronic inflammatory skin disease characterised by localised or generalised loss of skin pigmentation due to loss of epidermal melanocytes. Melanocyte homeostasis involving melanocyte stem cells, melanoblasts and differentiated interfollicular and hair follicle melanocytes play an important role in repigmentation in vitiligo. Our laboratory performed scRNAseq on cKit +ve human epidermal melanocytes purified by flow cytometry and identified a subpopulation of melanocytes which exhibited increased neutrotrophic receptor kinase 2 (NTRK2) expression and progenitor cell features as well as melanocytes expressing clusterin (CLU) associated with apoptosis. We sought to explore the role of melanocyte subpopulations in vitiligo affected skin.
Methods:
Skin biopsy samples from patients with vitiligo were obtained from the Vitiligo Clinic at the Skin Health Institute, Carlton, Victoria, Australia. Lesional skin was taken from depigmented lesions, and perilesional skin was taken from normally pigmented skin at the edge of the vitiligo lesions (AH-HREA74519). Immunofluoresence staining for dopachrome tautomerase (DCT) and NTRK2 was performed on formalin-fixed, paraffin-embedded sections. Analysis of NTRK2 and CLU melanocytes from published scRNAseq data of human vitiligo skin (DOI: 10.1126/scitranslmed.abd8995) was performed.
Results:
A disproportionate reduction in NTRK2+ melanocytes was observed in vitiligo skin compared to healthy normal skin controls and perilesional normally pigmented skin. Additionally, analysis of published scRNAseq dataset derived from vitiligo skin, perilesional skin and healthy control skin also demonstrate loss of NTRK2+ and CLU+ melanocytes. Other molecular markers expressed in NTRK2+ and CLU+ melanocytes are also reduced in vitiligo lesions, suggesting that remaining melanocytes are more likely terminally differentiated melanocytes rather than progenitors.
Conclusion:
Vitiligo affected skin are selectively depleted of specific melanocyte subpopulations, particularly those with progenitor features. This may represent a key biological process in the pathogenesis of vitiligo and explain inadequate therapeutic response in some patients to treatments such as UVB therapy.