Expansion of vitiligo lesions is associated with reduced epidermal CDw60 expression and increased expression of HLA-DR in perilesional skin

Poole, I. Caroline Le; Stennett, Lawrence; Bonish, Brian K.; Dee, Lars van; Robinson, June K.; Hernandez, Claudia; Hann, Seung Kyung; Nickoloff, Brian J.

doi:10.1046/j.1365-2133.2003.05539.x

Cited by 37 publications

(35 citation statements)

References 36 publications

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“…We found that IFN-γ inducible CDw60, representative of the ganglioside GD3, was upregulated in perilesional skin [36]. The type 1 cytokine profile observed for T cells isolated directly from depigmenting lesions likewise supports a T cell mediated autoimmune response.…”

Section: Involvement Of T Cells In Depigmentationsupporting

confidence: 57%

Therapeutic implications of autoimmune vitiligo T cells

Oyarbide-Valencia¹,

Boorn²,

Denman³

et al. 2006

Autoimmunity Reviews

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Vitiligo is an autoimmune disease presenting with progressive loss of skin pigmentation. The disease strikes 1% of the world population, generally during teenage years. The progressive loss of melanocytes from depigmenting vitiligo skin is accompanied by cellular infiltrates containing both CD4+ and CD8+ T lymphocytes. Infiltrating cytotoxic T cells with high affinity T cell receptors have likely escaped clonal deletion in the thymus, allowing such T cells to enter the circulation. Through the expression of CLA, these T cells home to the skin where they express type 1-cytokine profiles and mediate melanocyte apoptosis via the granzyme/perforin pathway. T cells found juxtapositionally apposed to remaining melanocytes can be isolated from the skin. Vitiligo T cells have demonstrated reactivity to antigens previously recognized as target antigens for T cells infiltrating melanoma tumors. In a comparison to existing melanoma-derived T cells, vitiligo T cells displayed superior reactivity towards melanoma cells. It is thought that genes encoding the TCRs expressed by vitiligo skin infiltrating T cells can be cloned and expressed in melanoma T cells, thereby generating a pool of circulating T cells with high affinity for their targets that can redirect the immune response towards the tumor.

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Section: Involvement Of T Cells In Depigmentationsupporting

confidence: 57%

Therapeutic implications of autoimmune vitiligo T cells

Oyarbide-Valencia¹,

Boorn²,

Denman³

et al. 2006

Autoimmunity Reviews

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“…variety of cytokines, most notably IFN-g (Barreto et al, 2003). The latter cytokine is generated in perilesional vitiligo skin by infiltrating T cells (Le Poole et al, 2003;WankowiczKalinska et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

4-Tertiary Butyl Phenol Exposure Sensitizes Human Melanocytes to Dendritic Cell-Mediated Killing: Relevance to Vitiligo

Kroll

Bommiasamy

Boissy

et al. 2005

Journal of Investigative Dermatology

151

125

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The trigger initiating an autoimmune response against melanocytes in vitiligo remains unclear. Patients frequently experience stress to the skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used as a model compound to study the effects of stress on melanocytes. Heat shock protein (HSP)70 generated and secreted in response to 4-TBP was quantified. The protective potential of stress proteins generated following 4-TBP exposure was examined. It was studied whether HSP70 favors dendritic cell (DC) effector functions as well. Melanocytes were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in response to 4-TBP exposure was partially released into the medium by immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70 in turn induced membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and activation of DC effector functions towards stressed melanocytes. Melanocytes exposed to 4-TBP demonstrated elevated TRAIL death receptor expression. DC effector functions were partially inhibited by blocking antibodies to TRAIL. TRAIL expression and infiltration by CD11c+ cells was abundant in perilesional vitiligo skin. Stressed melanocytes may mediate DC activation through release of HSP70, and DC effector functions appear to play a previously unappreciated role in progressive vitiligo.

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“…19-23 Moreover, the reduced expression of GD3 (which contributes to keratinocyte apoptosis) induces a compensatory mechanism of epidermal thickening to protect the affected skin from UV radiation damage. 23 Finally, two recent retrospective studies have not detected a statistically significant increase of non- melanoma skin cancer (first study) or non-melanoma and melanoma skin cancers (second study) in patients with vitiligo, compared to the general population. Moreover, this last retrospective study, did not found a trend of increasing prevalence of these skin cancers in the subgroup of patients treated with PUVA and Narrow-Band UVB, adjusted for age and time of exposure during life.…”

Section: Epidemiological Aspectsmentioning

confidence: 99%

Vitiligo - Part 1

Tarlé

Nascimento

Mira

et al. 2014

An. Bras. Dermatol.

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Vitiligo is a chronic stigmatizing disease, already known for millennia, which mainly affects melanocytes from epidermis basal layer, leading to the development of hypochromic and achromic patches. Its estimated prevalence is 0.5% worldwide. The involvement of genetic factors controlling susceptibility to vitiligo has been studied over the last decades, and results of previous studies present vitiligo as a complex, multifactorial and polygenic disease. In this context, a few genes, including DDR1, XBP1 and NLRP1 have been consistently and functionally associated with the disease. Notwithstanding, environmental factors that precipitate or maintain the disease are yet to be described. The pathogenesis of vitiligo has not been totally clarified until now and many theories have been proposed. Of these, the autoimmune hypothesis is now the most cited and studied among experts. Dysfunction in metabolic pathways, which could lead to production of toxic metabolites causing damage to melanocytes, has also been investigated. Melanocytes adhesion deficit in patients with vitiligo is mainly speculated by the appearance of Köebner phenomenon, recently, new genes and proteins involved in this deficit have been found.

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Expansion of vitiligo lesions is associated with reduced epidermal CDw60 expression and increased expression of HLA-DR in perilesional skin

Abstract: These results support an active role of melanocytes within the skin immune system, and associate their loss in generalized vitiligo with a cell-mediated immune response mediated by type 1 cytokines.

Cited by 37 publications

References 36 publications

Therapeutic implications of autoimmune vitiligo T cells

Therapeutic implications of autoimmune vitiligo T cells

4-Tertiary Butyl Phenol Exposure Sensitizes Human Melanocytes to Dendritic Cell-Mediated Killing: Relevance to Vitiligo

Vitiligo - Part 1

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