The Role of Oxidative Stress in Vitiligo: An Update on Its Pathogenesis and Therapeutic Implications

Abstract

Vitiligo is an autoimmune skin disorder caused by dysfunctional pigment-producing melanocytes which are attacked by immune cells. Oxidative stress is considered to play a crucial role in activating consequent autoimmune responses related to vitiligo. Melanin synthesis by melanocytes is the main intracellular stressor, producing reactive oxygen species (ROS). Under normal physiological conditions, the antioxidative nuclear factor erythroid 2-related factor 2 (Nrf2) pathway functions as a crucial mediator for cells to resist oxidative stress. In pathological situations, such as with antioxidant defects or under inflammation, ROS accumulate and cause cell damage. Herein, we summarize events at the cellular level under excessive ROS in vitiligo and highlight exposure to melanocyte-specific antigens that trigger immune responses. Such responses lead to functional impairment and the death of melanocytes, which sequentially increase melanocyte cytotoxicity through both innate and adaptive immunity. This report provides new perspectives and advances our understanding of interrelationships between oxidative stress and autoimmunity in the pathogenesis of vitiligo. We describe progress with targeted antioxidant therapy, with the aim of providing potential therapeutic approaches.

Exploring the roles and potential therapeutic strategies of inflammation and metabolism in the pathogenesis of vitiligo: a mendelian randomization and bioinformatics-based investigation

“…Current research suggests that vitiligo results from the combined effects of genetic factors (approximately 80%) and environmental stressors (about 20%) ( Bergqvist and Ezzedine, 2021 ). Under this interplay, melanocytes in vitiligo patients are more susceptible to oxidative stress, leading to cellular damage ( Jadeja et al, 2020 ; Chang and Ko, 2023 ). This process prompts melanocytes to release exosomes containing specific antigens, activating CD8 + T cells to produce various cytokines such as IFNγ, TNF, and GZMB.…”

Dietary habits in adult Japanese patients with vitiligo

“…Vitiligo is an autoimmune skin disorder characterized by depigmented patches due to the dysfunctional melanocytes attacked by immune cells 1 . The pathogenesis of vitiligo is multifactorial, related to melanocyte dysfunction by genetic susceptibility, dysregulated oxidative stress, inflammation, and autoimmune responses 2 .…”

“…The melanocytes that have died release autoantigens, such as gp100, which are carried by DCs and presented to autoreactive CTLs. Autoreactive CTLs release perforin and granzyme B, inducing apoptosis of melanocytes, 2 and IFN‐γ and TNF‐α, inducing the detachment of melanocytes from keratinocytes by reducing E‐cadherin expression 1 . The CD8+CD103+CD69+CD49a+ resident memory T cells (T RM ) and keratinocyte‐derived IL‐15, a cytokine sustaining T RM , contribute to the perpetuation and recurrence of vitiligo 2,5,6 …”

An Evaluation of the Hematological Markers of Systemic Inflammation and Oxidative Stress in Vitiligo: A Case-Control Study

“…Segmental vitiligo typically occurs in childhood and affects only one area of the body. Nonsegmental vitiligo is classified into acrofacial, mucosal, generalized, universal, mixed, and rare variants according to the area and extent of involvement [ 3 ].…”

“…ROS overproduction in melanocytes can lead to the formation of autoantigens, which may trigger adaptive and cellular immunity [ 3 ]. Dendritic cells and macrophages are activated by autoantigens, resulting in T-cell activation.…”