Vitiligo is an autoimmune skin disease characterized by the targeted destruction of melanocytes by T cells. Cytokine signaling between keratinocytes and T cells results in CD8⁺ T cell infiltration of vitiligo lesions, but the full scope of signals required to coordinate autoimmune responses is not completely understood. We performed single-cell RNA sequencing on affected and unaffected skin from patients with vitiligo, as well as healthy controls, to define the role of each cell type in coordinating autoimmunity during disease progression. We confirmed that type 1 cytokine signaling occupied a central role in disease, but we also found that this pathway was used by regulatory T cells (T_regs) to restrain disease progression in nonlesional skin. We determined that CCL5-CCR5 signaling served as a chemokine circuit between effector CD8⁺ T cells and T_regs, and mechanistic studies in a mouse model of vitiligo revealed that CCR5 expression on T_regs was required to suppress disease in vivo but not in vitro. CCR5 was not required for T_reg recruitment to skin but appeared to facilitate T_reg function by properly positioning these cells within the skin. Our data provide critical insights into the pathogenesis of vitiligo and uncover potential opportunities for therapeutic interventions.

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人类白癜风的 scRNA-seq 揭示了亚临床免疫激活的复杂网络以及 CCR5 在 Treg 功能中的作用

白癜风是一种自身免疫性皮肤病，其特征是T细胞靶向破坏黑色素细胞。角质形成细胞和 T 细胞之间的细胞因子信号传导导致 CD8 ⁺ T 细胞浸润白斑病灶，但尚未完全了解协调自身免疫反应所需的全部信号范围。我们对白癜风患者以及健康对照的受影响和未受影响的皮肤进行了单细胞 RNA 测序，以确定每种细胞类型在疾病进展过程中在协调自身免疫中的作用。我们证实 1 型细胞因子信号传导在疾病中起核心作用，但我们还发现该途径被调节性 T 细胞（T _regs) 以抑制非损伤性皮肤的疾病进展。我们确定 CCL5-CCR5 信号作为效应 CD8 ⁺ T 细胞和 T _regs之间的趋化因子回路，并且在白癜风小鼠模型中的机制研究表明，T _regs上的 CCR5 表达是抑制体内疾病而不是体外抑制疾病所必需的。_{CCR5 对皮肤的 T reg}募集不是必需的，但似乎通过将这些细胞正确定位在皮肤内来促进 T _reg功能。我们的数据提供了对白癜风发病机制的重要见解，并揭示了治疗干预的潜在机会。