Vitiligo is an autoimmune skin disease in which epidermal melanocytes are targeted for destruction by CD8⁺ T cells specific for melanocyte/melanoma-shared antigens. IFNγ is the central cytokine driving disease, but the role of type I IFN in vitiligo remains unclear. We investigated the functional role of type I IFN during vitiligo progression using two different mouse models: one induced with a vaccinia virus (VV) vaccine and one induced with dendritic cells to prime autoimmune T cells. Induction of vitiligo by VV in IFNaR-deficient mice led to the development of severe vitiligo compared with wild-type (WT) mice and was characterized by a significantly enhanced effector CD8⁺ T-cell response. Severe vitiligo in this model was a result of VV persistence, because exacerbation of disease in IFNaR-deficient mice was not observed when antigen-pulsed dendritic cells were used to induce vitiligo instead of virus. Treatment of B16F10 melanoma-inoculated mice with VV vaccine therapy also induced a significantly enhanced anti-tumor response in IFNaR-deficient mice compared with WT. These results not only help define the pathways responsible for vitiligo progression but also suggest that blockade of type I IFNs following administration of a VV vaccine may provide increased immunogenicity and efficacy for melanoma immunotherapy.

中文翻译：

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在白癜风和黑色素瘤免疫治疗开始期间，I 型干扰素信号限制了 CD8+ T 细胞的病毒载体启动

白癜风是一种自身免疫性皮肤病，其中表皮黑色素细胞被针对黑色素细胞/黑色素瘤共有抗原特异性的 CD8 ^{+ T 细胞破坏。}IFNγ 是中枢细胞因子驱动疾病，但 I 型 IFN 在白癜风中的作用仍不清楚。我们使用两种不同的小鼠模型研究了 I 型 IFN 在白癜风进展过程中的功能作用：一种用牛痘病毒 (VV) 疫苗诱导，另一种用树突状细胞诱导以引发自身免疫 T 细胞。与野生型 (WT) 小鼠相比，VV 在 IFNaR 缺陷小鼠中诱导白癜风导致严重白癜风的发展，其特征是效应子 CD8 ^{+显着增强}T细胞反应。该模型中的严重白癜风是 VV 持续存在的结果，因为当使用抗原脉冲的树突状细胞而不是病毒诱导白癜风时，没有观察到 IFNaR 缺陷小鼠的疾病恶化。与 WT 相比，用 VV 疫苗治疗接种 B16F10 黑色素瘤的小鼠也诱导了 IFNaR 缺陷小鼠的抗肿瘤反应显着增强。这些结果不仅有助于确定导致白癜风进展的途径，而且还表明在施用 VV 疫苗后阻断 I 型 IFN 可以提高黑色素瘤免疫治疗的免疫原性和功效。