Characterization of PLP1+ cells and natural killer cells with heightened activity in vitiligo

Background: Vitiligo is a complex autoimmune skin condition characterized by the death of melanocytes, the principle pigment producing cells in the skin. Transcriptome analysis of vitiligo skin revealed significantly reduced levels of proteolipid 1 (PLP1) gene, which is known to be expressed by Schwann cells, as well as significantly up-regulation of genes that are associated with natural killer (NK) cell activity. Hypothesis and Objectives: Schwann cells may be adversely affected in vitiligo and NK cells may potentially play a role in the overall disease pathogenesis. Therefore, the purpose of this study is to characterize the down-regulation of PLP1 and assess the presence of NK cell infiltration in vitiligo skin biopsies. Materials and Methods: PLP1 expression analyses were performed on major types of skin cells as well as vitiligo and normal skin samples. Quantification of Schwann cells was performed on paired vitiligo samples using immunohistochemistry. Schwann cell conditioned medium was also tested for its ability to support the growth and survival of human melanocytes. To assess NK cell activity, explant skin cultures and immunofluorescence analyses were performed to localize activated NK cells in skin biopsies. Results: Schwann cells were the primary source of PLP1 in human skin, although it is also expressed by melanocytes. Schwann cells were found to be decreased in vitiligo lesional skin as compared to peri-lesional and normal skin. In addition, conditional medium prepared from cultured Schwann cells significantly increased the survival of human melanocytes. Furthermore, explant skin cultures and immunofluorescence studies revealed marked increase of NK cells with heightened activity in vitiligo lesional as well as peri-lesional vitiligo skin. Conclusion: Results from our study suggest that the loss of melanocytes and reduction in Schwann cells may account for the down-regulation of PLP1 in vitiligo lesional skin. In addition, Schwann cells may play a role in the growth and survival of melanocytes and their decrease may have facilitated the development of vitiligo. Furthermore, this study lends support to the direct involvement of NK cells in the pathogenesis of vitiligo and suggests that they should be explored as cellular targets for development of better therapies in the future.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat