Immune responses in a mouse model of vitiligo with spontaneous epidermal de‐ and repigmentation

Summary To generate a mouse model of spontaneous epidermal depigmentation, parental h3 TA 2 mice, expressing both a human‐derived, tyrosinase‐reactive T‐cell receptor on T cells and the matching HLA ‐A2 transgene, were crossed to keratin 14‐promoter driven, stem cell factor transgenic (K14‐ SCF ) mice with intra‐epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical and sharply demarcated patches of graying hair. Whereas the SCF transgene alone dictates a greater retinoic acid receptor‐related orphan receptor gamma ( ROR γt) + T‐cell compartment, these cells displayed markedly increased IL ‐17 expression within Vitesse mice. Similar to patient skin, regulatory T cells were less abundant compared with K 14‐ SCF mice, with the exception of gradually appearing patches of repigmenting skin. The subtle repigmentation observed likely reflects resilient melanocytes that coexist with skin‐infiltrating, melanocyte‐reactive T cells. Similar repigmenting lesions were found in a different TCR transgenic model of vitiligo developed on an SCF transgenic background, supporting a role for SCF in repigmentation.