Abstract：
We have discovered that human vitiligo patients treated with narrow-band UVB (NBUVB) demonstrated localized resistance to repigmentation in skin sites characterized by distinct cellular and molecular pathways. Using immunostaining studies, discovery-stage RNA-Seq analysis, and confirmatory in situ hybridization, we analyzed paired biopsies collected from vitiligo lesions that did not repigment after 6 months of NBUVB treatment (non-responding) and compared them with repigmented (responding) lesions from the same patient. Non-responding lesions exhibited acanthotic epidermis, had low number of total, proliferative, and differentiated melanocyte (MC) populations, and increased number of senescent keratinocytes (KCs) and of cytotoxic CD8+ T cells as compared with responding lesions. The abnormal response in the non-responding lesions was driven by a dysregulated cAMP pathway and of upstream activator PDE4B, and of WNT/β-catenin repigmentation pathway. Vitiligo-responding lesions expressed high levels of WNT10B ligand, a molecule that may prevent epidermal senescence induced by NBUVB, and that in cultured melanoblasts prevented the pro-melanogenic effect of α-MSH. Understanding the pathways that govern lack of NBUVB-induced vitiligo repigmentation has a great promise in guiding the development of new therapeutic strategies for vitiligo.
摘要：
我们发现，用窄带UVB（NBUVB）治疗的人类白癜风患者在皮肤部位表现出对色素沉着的局部抗性，其特征在于不同的细胞和分子途径。使用免疫染色研究，发现阶段RNA-Seq分析，和确证原位杂交，我们分析了从NBUVB治疗6个月后未发生色素沉着(无反应)的白癜风病变收集的配对活检,并将其与同一患者的色素沉着(有反应)病变进行比较.无反应病变表现为棘皮表皮，总数低，增殖性,和分化的黑素细胞（MC）群体，与响应性病变相比，衰老角质形成细胞（KCs）和细胞毒性CD8T细胞的数量增加。无反应病变中的异常反应是由cAMP通路和上游激活剂PDE4B的失调驱动的，和WNT/β-catenin再色素沉着途径。白癜风反应性病变表达高水平的WNT10B配体，一种可以防止NBUVB诱导的表皮衰老的分子，并且在培养的黑素细胞中阻止了α-MSH的促黑色素生成作用。了解控制缺乏NBUVB诱导的白癜风色素沉着的途径在指导白癜风新治疗策略的开发方面具有很大的希望。
