Vitiligo: An Autoimmune Skin Disease and its Immunomodulatory Therapeutic Intervention

Abstract

Vitiligo is a chronic autoimmune depigmenting skin disorder characterized by patches of the skin losing functional melanocytes. Multiple combinatorial factors are involved in disease development, among which immune T cells play a prominent role. The immune cells implicated in melanocyte destruction through adaptive immunity include CD8+ cytotoxic T cells and regulatory T cells, and aberrantly activated skin-resident memory T cells also play a role in melanocyte destruction. Over the past several years, major progress in understanding vitiligo pathogenesis has led to the development of targeted therapies. Janus kinase (JAK) inhibitors, which share the similar mechanism that autoactivates CD8+ T cells in chronic inflammatory diseases, have been reported to have therapeutic significance in vitiligo. Recently, immunomodulatory therapeutic interventions in vitiligo have been emerging. Mesenchymal stem cells (MSCs) regulate cytokine secretion and the balance of T-cell subsets, which makes them a promising cell-based treatment option for autoimmune diseases. The induction of MSC-mediated immunomodulation is complicated and occurs by contact-dependent mechanisms and soluble extracellular vesicle (EV) mediators. EVs released from MSCs contain various growth factors and cytokines with anti-inflammatory effects in the skin immune response. Here, we summarize and discuss the progress to date in targeted therapies that immunomodulate the niche environment of vitiligo, from the clinical trial of JAK inhibitors to the potential of MSCs and MSC-EVs. The available information was collected to highlight the need for further research into the treatment of vitiligo.

Generation of Pmel‐dependent conditional and inducible Cre‐driver mouse line for melanocytic‐targeted gene manipulation

“…Vitiligo is an autoimmune disease in which melanocytes are destructed by autoreactive T cells, forming patches of unpigmented skin (Chang et al, 2021). In patients with vitiligo, melanocyte‐reactive T cells that recognize melanocyte differentiation antigens, including MLANA, TYR, and PMEL, are frequently found in perilesional skin and peripheral blood (Ongenae et al, 2003).…”

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

“…Cytotoxic T lymphocytes can induce cytotoxicity in melanocytes directly by releasing mediators such as TNF-α and IFN-γ. When IFN-γ binds to its receptor, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is activated and stimulates the transcription of the chemokine ligands CXCL9 and CXCL10 [ 53 ]. This creates a positive feedback loop for T-cell recruitment and function [ 53 ].…”

“…When IFN-γ binds to its receptor, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is activated and stimulates the transcription of the chemokine ligands CXCL9 and CXCL10 [ 53 ]. This creates a positive feedback loop for T-cell recruitment and function [ 53 ]. The levels of IFN-γ were reported to be elevated in lesional skin of patients with vitiligo [ 54 ], which induced an increase of CXCL10 in vitiligo melanocytes [ 55 ].…”

Comments on “Anatomically distinct fibroblast subsets determine skin autoimmune patterns”

“…Keratinocytes were thought to be predominantly responsible for T cell recruitment and they were considered to produce the bulk of chemokines. [ 3 , 4 ] Few researchers pay attention to the pivotal role of fibroblasts in the pathogenesis of immunity in vitiligo. This study identified that IFNγ-responsive fibroblasts can recruit CD8 + T cells through CXCL9 and CXCL10 in vitiligo.…”

“…This study sufficiently identified the positive-feedback loop between IFNγ-responsive fibroblasts and CD8 + T cells in vitiligo. Keratinocytes were thought to be predominantly responsible for T cell recruitment and they were considered to produce the bulk of chemokines [3,4] . Few researchers pay attention to the pivotal role of fibroblasts in the pathogenesis of immunity in vitiligo.…”