Vitiligo is a pigmentary skin disease resulting from T cell mediated cytotoxicity towards melanocytes. To study the involvement of Th17 cells in vitiligo pathogenesis, we generated a spontaneous mouse model of epidermal depigmentation in vitiligo by crossing HLA-A2 transgenic mice expressing a human-derived, tyrosinase reactive T cell receptor transgene within T cells were crossed with a K14-SCF transgenic mouse that retains intra-epidermal melanocytes. In this triple (HLA-A2, h3T, K14-SCF) transgenic mouse, we observed that hair depigmentation was significantly accelerated as compared to the h3TA2 mice parental strain. The presence of the SCF transgene is associated with an increase of IL-17A+T cells among peripheral T cells. Triple transgenic display enhanced tyrosinase-specific Th17 responses and stronger spontaneous CTL responses. The increased Th17 responses are correlated to expansion of SCF responsive MM cell for megakaryocyte and/or bipotent megakaryocyte/erythroid progenitors (CD117+CD151+CD41+CD11c-CD11b-) that induce Th17 cells as previously shown to mediate lupus. In addition, SCF overexpression allows for spotted repigmentation of the epidermis to form ‘NeVi’. Repigmentation is accompanied by reduced Th17 and increased Treg infiltration to the skin. Taken together, accelerated vitiligo is associated with IL-17 responses in mice.
- Copyright © 2013 by The American Association of Immunologists, Inc.