University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA; email:
Annu Rev Immunol. 2020 Apr 26;38:621-648. doi: 10.1146/annurev-immunol-100919-023531. Epub 2020 Feb 4.
Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Autoreactive cytotoxic CD8 T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin through a positive-feedback loop. Both topical and systemic treatments that block IFN-γ signaling can effectively reverse vitiligo in humans; however, disease relapse is common after stopping treatments. Autoreactive resident memory T cells are responsible for relapse, and new treatment strategies focus on eliminating these cells to promote long-lasting benefit. Here, we discuss basic, translational, and clinical research studies that provide insight into the pathogenesis of vitiligo, and how this insight has been utilized to create new targeted treatment strategies.
白癜风是一种皮肤自身免疫性疾病，其靶标是产生色素的黑素细胞，导致可见的脱色斑块，呈现为白色斑点。最近的研究深入了解了这种疾病的发病机制。自身反应性细胞毒性 CD8 T 细胞与黑素细胞结合，并通过局部产生 IFN-γ 促进疾病进展，IFN-γ 诱导的趋化因子随后从周围角质形成细胞分泌，通过正反馈循环进一步将 T 细胞招募到皮肤中。阻断 IFN-γ 信号的局部和全身治疗都可以有效地逆转人类的白癜风；然而，停止治疗后疾病常复发。自身反应性常驻记忆 T 细胞是复发的原因，新的治疗策略集中在消除这些细胞以促进长期获益。在这里，我们讨论了基础、转化和临床研究，这些研究提供了对白癜风发病机制的深入了解，以及如何利用这些见解来创建新的靶向治疗策略。
