Oncology Research Institute, Loyola University Chicago, Chicago, IL, USA.
Pigment Cell Melanoma Res. 2014 Nov;27(6):1075-85. doi: 10.1111/pcmr.12284. Epub 2014 Jul 21.
To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 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 (RORγt)(+) 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 K14-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.
为了生成自发性表皮脱色的小鼠模型，表达在 T 细胞上的人类来源的酪氨酸酶反应性 T 细胞受体和匹配的 HLA-A2 转基因的亲本 h3TA2 小鼠与表皮内黑素细胞的角质形成细胞 14 启动子驱动的干细胞因子转基因（K14-SCF）小鼠交配。在产生的 Vitesse 小鼠中，自发性皮肤脱色先于对称和明显界定的灰白色毛发斑块。虽然单独的 SCF 转基因决定了更大的视黄酸受体相关孤儿受体γ（RORγt）（+）T 细胞区室，但这些细胞在 Vitesse 小鼠中显示出明显增加的 IL-17 表达。与 K14-SCF 小鼠相比，调节性 T 细胞的数量较少，除了逐渐出现的复色皮肤斑块外。观察到的微妙复色可能反映了与皮肤浸润的黑素细胞反应性 T 细胞共存的有弹性的黑素细胞。在基于 SCF 转基因的另一种 T 细胞受体转基因白癜风模型中也发现了类似的复色病变，支持 SCF 在复色中的作用。
