Genetic and immune dysregulation in vitiligo: Insights into autoimmune mechanisms and disease pathogenesis

Vitiligo is a hypopigmentary skin disease condition affecting local melanocytes leading to the white patched/macules of depigmented skin due to their progressive loss of melanocytes in the epidermis. Vitiligo pathogenesis involves complex interaction of several trigger factors including genetic predispositions, environmental stimuli, oxidative stress, immunological dysregulation, and impaired melanocyte function. Genetic studies have provided insight into the essential aspects related to immunological modulation, melanocyte biology and the oxidative stress response, aiding in understanding the possible mechanisms underlying vitiligo susceptibility. Epigenetic modifications further contribute to the regulatory landscape controlling the pathophysiology of this disease. While genetic studies identified key susceptibility loci, it is the functional studies that have driven the development of novel targeted therapies. Although vitiligo exhibits complex heterogenous clinical manifestations and multiple contributing factors, significant advancements have been achieved in understanding the underlying mechanism of the disease. Particularly, cytotoxic T-cell activity and interferon-gamma (IFN-ϒ) mediated immune response have been studied extensively in disease pathogenesis. This has led to the development of novel targeted therapies including cytokine targeted therapies, Janus-activated kinase (JAK) signaling inhibitors, and Wnt signaling agonists which have shown potential clinical success.