Mechanisms of melanocyte death in vitiligo

Abstract

Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation. Genome‐wide associated studies have identified single‐nucleotide polymorphisms in a panel of susceptible loci as risk factors in melanocyte death. But vitiligo onset can't be solely attributed to a susceptive genetic background. Oxidative stress triggered by elevated levels of reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, a minority of melanocyte demise, and melanocyte‐specific antigens exposure. Of note, the self‐responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo. The aberrantly heightened innate immunity, type‐1‐skewed T helper, and incompetent regulatory T cells tip the balance toward autoreaction and CD8+ cytotoxic T lymphocytes finally execute the killing of melanocytes, possibly alarmed by resident memory T cells. In addition to the well‐established apoptosis and necrosis, we discuss several death modalities like oxeiptosis, ferroptosis, and necroptosis that are probably employed in melanocyte destruction. This review focuses on the various mechanisms of melanocytic death in vitiligo pathogenesis to demonstrate a panorama of that. We hope to provide new insights into vitiligo pathogenesis and treatment strategies by the review.

Development of a Multi-Target Strategy for the Treatment of Vitiligo via Machine Learning and Network Analysis Methods

“…On the other hand, TXN was highly expressed in vitiligo skin samples ( Figure 5 ) and controlled the cellular redox environment ( Lu and Holmgren, 2014 ). And previous studies had demonstrated that oxidative stress was critical for the progression of vitiligo ( Chang et al, 2017 ; Ma et al, 2018 ; Yi et al, 2019 ; Chen et al, 2021 ). However, there was no study to report the relationship between TXN and vitiligo, which attracted our attention.…”

TLR4 gene polymorphisms in Egyptian vitiligo patients: insights into emerging association with clinical activity, family history, and response to therapy

“…TLR4 is expressed on melanocytes and believed to react to endogenous heat-shock proteins and initiate autoimmunity [ 20 ] by stimulating dendritic cells (DCs) to present melanocyte-specific antigens to T cells in lymphoid tissues [ 21 ]. Activated DCs release a cascade of cytokines that stimulate keratinocytes and activated NK cells together with chemo-attracted melanocyte-specific CD8 + T cells leading to the T cell-mediated autoimmune destruction of melanocytes [ 22 ].…”

Short Overview of Some Assays for the Measurement of Antioxidant Activity of Natural Products and Their Relevance in Dermatology

“…Alterations in the glutathione system, one of the major endogenous antioxidant defenses, were reported for alopecia areata [ 58 ], psoriasis [ 65 ], oral lichen planus [ 70 ] and atopic dermatitis [ 73 ]. In addition, vitiligo is also accompanied by decreased antioxidant defenses [ 67 ] and elevated oxidation products [ 68 , 69 ] that mediate the death of melanocytes [ 74 ]. Deregulated redox homeostasis and oxidation of macromolecules further accompany cutaneous disease pathology [ 40 , 61 , 68 , 71 ].…”