Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: role of SCF/KIT protein interactions and the downstream effector, MITF‐M

Abstract Little is known about the mechanisms involved in the dysfunction of melanocytes in vitiligo epidermis. It is hypothesized that some cytokine/receptor interactions may be affected, resulting in dysfunction and/or loss of melanocytes. This study has compared the expression of endothelin (ET)‐1, the ET‐1 receptor (ET B R), granulocyte macrophage colony stimulating factor (GM‐CSF), stem cell factor (SCF), the SCF receptor (KIT protein), tyrosinase, and S100α between lesional and non‐lesional vitiligo epidermis. Analysis by reverse transcription‐polymerase chain reaction (RT‐PCR) and by western blotting for ET‐1 and SCF unexpectedly demonstrated up‐regulated expression of these cytokines in lesional vitiligo epidermis. Immunohistochemistry with antibodies to melanocyte markers revealed that at the edge of the lesional epidermis, melanocytes remain and express tyrosinase, S100α and ET B R, but not KIT protein or melanocyte‐specific microphthalmia‐associated transcription factor (MITF‐M). Quantitation of the staining revealed a slight or moderate decrease in the number of S100α, tyrosinase, and ET B R‐positive cells at the edge of the lesional epidermis. In contrast, the number of cells expressing KIT protein was markedly decreased at the edge of the lesional epidermis compared with the non‐lesional epidermis. At the centre of the lesional epidermis, there was complete loss of melanocytes expressing KIT protein, S100α, ET B R, and/or tyrosinase. Western blotting revealed down‐regulated expression of c‐kit and MITF‐M proteins at the edge of the lesional epidermis in vitiligo. These findings suggest that reduction in the expression of KIT protein by melanocytes and its downstream effectors, including MITF‐M, may be associated with the dysfunction and/or loss of melanocytes in vitiligo epidermis. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.