New Insights into the Pathogenesis of Vitiligo: Imbalance of Epidermal Cytokines at Sites of Lesions

Abstract

Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.

PI3K mediates protection against TRAIL-induced apoptosis in primary human melanocytes

“…Interestingly, in vitiligo, a decreased level of SCF has been found in the depigmented zone, in which melanocytes were thought to die by apoptosis. 47,48 Further, SCF production by keratinocytes is increased by ultraviolet B (UVB) radiation, which is known to increase nevi size and number. 49,50 In the same line, transgenic mice expressing elevated levels of SCF develop melanocyte dysplasia.…”

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

“…A number of studies indicate that decreased TGFin vitiligo patients, and this could have a deleterious effect upon Treg cell function in these individuals [58][59][60]. In addition, serum concentrations of TGF-have been shown to be decreased in cases of active but not stable vitiligo, indicating that lower levels of the cytokine are positively correlated with disease progression [61].…”

Association of C-469T of Interleukin 13 Gene Polymorphism with Vitiligo Development in Thi Qar Province/South of Iraq

“…Several studies showed the role of peripheral blood and lesional cytokine expression in vitiligo patients. These suggested a role for epidermal cytokine imbalance in the pathogenesis of vitiligo [6,7].…”

“…Co-occurrence with autoimmune diseases seems to be dependent of the clinical type of vitiligo especially with nonsegmental type [2]; however, the observation is not as frequent when considering exclusively the segmental clinical type of vitiligo [4]. The changing in cytokines levels were reported in vitiligo affected skin compared with healthy skin suggesting that the cytokine production in epidermal microenvironment may play a role in pathogenesis of vitiligo [5,6]. Several studies showed the role of peripheral blood and lesional cytokine expression in vitiligo patients.…”