Type-1 cytokines regulate matrix metalloprotease-9 production and E-cadherin disruption to promote melanocyte loss in vitiligo

Boukhedouni, Nesrine; Martins, Christina; Darrigade, Anne‐Sophie; Drullion, Claire; Rambert, Jérôme; Barrault, C.; Garnier, Julien; Jacquemin, Clément; Thiolat, Denis; Lucchese, Fabienne; Morel, Franck; Ezzedine, Khaled; Taı̈eb, Alain; Bernard, François‐Xavier; Sénéschal, Julien; Boniface, Katia

doi:10.1172/jci.insight.133772

Cited by 57 publications

(73 citation statements)

References 58 publications

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“…Under oxidative stress, elevated Src kinase expression and altered lipid raft arrangement disrupt protein interaction of the β‐catenin with E‐cadherin on melanocyte surface, ultimately weaker melanocyte–keratinocyte adhesion and enhanced melanocyte detachment 87,88 . And the shedding of E‐cadherin seems to be precipitated also by type‐1 cytokines like interferon (IFN)‐γ and tumor necrosis factor (TNF)‐α through activated MMP‐9, according to a recent publication 89 . Furthermore, the detachment disrupts fibronectin adhesion‐mediated apoptosis suppression, and migrating to the upper layer of epidermis indicates more onslaught from deleterious stimulations like UV, both of which intensify melanocytes apoptosis and necrosis 90,91 .…”

Section: Oxidative Stressmentioning

confidence: 99%

Mechanisms of melanocyte death in vitiligo

Chen

2020

Medicinal Research Reviews

148

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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.

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Section: Oxidative Stressmentioning

confidence: 99%

Mechanisms of melanocyte death in vitiligo

Chen

2020

Medicinal Research Reviews

148

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“…When this paper was being reviewed, Boukhedouni et al 13 . described that the type 1 cytokines interferon‐γ and tumor necrosis factor‐α induced melanocyte detachment through E‐cadherin disruption and regulated matrix metallopeptidase‐9 production in vitiligo.…”

Section: Discussionmentioning

confidence: 99%

Expression of discoidin domain receptor 1 and E‐cadherin in epidermis affects melanocyte behavior in rhododendrol‐induced leukoderma mouse model

Abe

Hozumi

Okamura

et al. 2020

The Journal of Dermatology

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Vitiligo is a depigmentation disease characterized by gradual loss of melanin and melanocytes from the epidermis. The mechanism of melanocyte loss is not yet known. In this report, we showed that the expression of discoidin domain receptor 1 and E‐cadherin, known adhesion molecules, was variable or absent in the epidermis of rhododendrol‐induced leukoderma (RDIL) mice during the depigmentation process. Our findings suggest that melanocyte damage by rhododendrol promotes reduction of adhesion molecules not only in melanocytes but also in keratinocytes, and this is associated with the detachment of melanocytes from the basal layer.

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“…The interaction between melanocytes and keratinocytes is realized through cell‐to‐cell adhesion molecules such as E‐cadherin that has been shown to be decreased or absent in perilesional vitiligo skin (Delmas & Larue, 2019) which could result in melanocyte detachment as was first hypothesized (Gauthier et al., 2003). In recent work, Boukhedouni et al have elegantly shown that perilesional vitiligo skin is characterized by melanocyte detachment and that this event is generally followed by cell apoptosis (Boukhedouni et al., 2020). Moreover, they underline that this process is due to alteration of membrane E‐cadherin in response to increased production of metalloproteinase‐9 (MMP‐9) by keratinocytes under the influence of IFN‐γ and TNF‐α, characteristic cytokines of vitiligo (Regazzetti et al., 2015; Richmond, Bangari, et al, 2017).…”

Section: Non‐immunological Factors In Vitiligomentioning

confidence: 99%

An update on Vitiligo pathogenesis

Sénéschal

Boniface

D’Arino

et al. 2020

Pigment Cell Melanoma Res

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Vitiligo, the most common depigmenting disorder of the skin, is undergoing a period of intense advances in both disease understanding and therapeutic possibilities leading the way to the beginning of a new era for the disorder. Its pathophysiology has gathered the attention of researchers for years, and many advances have been made in the clarification of the interaction between different factors that result in depigmented macule formation. The complex interplay between non‐immunological and immunological factors in vitiligo is key for the development of the disease, and the participation of cells other than melanocytes, such as keratinocytes, fibroblasts, natural killer cells, and innate lymphoid cells, has been shown. Recent advances have also brought to the understanding of the complex part played by a specific subtype of T cells: T‐resident memory cells. This review analyzes some of the most recent insights in vitiligo pathogenesis underlining the interactions between different cell types, which are the basis for the therapeutic approaches under development.

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Type-1 cytokines regulate matrix metalloprotease-9 production and E-cadherin disruption to promote melanocyte loss in vitiligo

Cited by 57 publications

References 58 publications

Mechanisms of melanocyte death in vitiligo

Mechanisms of melanocyte death in vitiligo

Expression of discoidin domain receptor 1 and E‐cadherin in epidermis affects melanocyte behavior in rhododendrol‐induced leukoderma mouse model

An update on Vitiligo pathogenesis

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