Vitiligo: Mechanisms of Pathogenesis and Treatment

Abstract

Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Autoreactive cytotoxic CD8+ T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin through a positive-feedback loop. Both topical and systemic treatments that block IFN-γ signaling can effectively reverse vitiligo in humans; however, disease relapse is common after stopping treatments. Autoreactive resident memory T cells are responsible for relapse, and new treatment strategies focus on eliminating these cells to promote long-lasting benefit. Here, we discuss basic, translational, and clinical research studies that provide insight into the pathogenesis of vitiligo, and how this insight has been utilized to create new targeted treatment strategies.

Antigen Specificity Enhances Disease Control by Tregs in Vitiligo

“…The prevalence of vitiligo is 0.5-1%, and this disorder is associated with low self-esteem, psychological stress, and social stigma (3)(4)(5). Therapies currently available for vitiligo have limited efficacy, and a real need for new treatment strategies exists (6). Several factors contribute to the pathogenesis of vitiligo.…”

Intratumoral virotherapy with 4-1BBL armed modified vaccinia Ankara eradicates solid tumors and promotes protective immune memory

“…Vitiligo is a pigmentation disorder with focal loss of melanocytes in the skin caused by autoreactive CD8 + T cells. 50 These cells have been induced by IT MVA-TAA-4-1BBL virotherapy, most likely through antigen spread, a phenomenon that describes the diversification of epitope specificity from the initial focused, dominant epitope-specific immune response, for example, Gp70 or OVA. In support of this hypothesis, IT MVA-OVA-4-1BBL cured mice that were rechallenged with B16.F10 tumor cells lacking the primary rejection antigen OVA showed significantly prolonged survival compared with naïve mice.…”

An Update on the Potential of Mesenchymal Stem Cell Therapy for Cutaneous Diseases

“…Vitiligo and alopecia areata (AA) are common chronic and recurrent autoimmune skin disorders characterized by white spots on the skin (vitiligo) and bald spots on the scalp (AA) because of selective destruction of melanocytes (MC) [ 2 , 59 , 60 ]. Most recently, Zhu et al [ 60 ] found that vitiligo patients present with a high level of PTEN expression that may contribute to the impairment of melanocytes.…”