Immune dysregulation is critical in vitiligo pathogenesis. Although the presence and roles of numerous CD4⁺ T-cell subsets have been described, the presence of Th9 cells and more importantly, roles of IL-9 on melanocyte functions are not explored yet. Here, we quantified the T helper cell subsets including Th9 cells in vitiligo patients by multicolor flowcytometry. There was an increased frequency of skin-homing (CLA⁺) and systemic (CLA^-) Th9 cells in vitiligo patients compared to healthy donors. However, there was no difference in Th9 cell frequency in vitiligo patients with early and chronic disease. There was negligible IL-9 receptor (IL-9R) expression on human primary melanocytes (HPMs); however, IFNγ upregulated IL-9R expression on HPMs. Functionally, IL-9/IL-9R signaling reduced the production of IFNγ-induced toxic reactive oxygen species (ROS) in HPMs. There was no effect of IL-9 on expression of genes responsible for melanosome formation (MART1, TYRP1, and DCT), melanin synthesis (TYR), and melanocyte-inducing transcription factor (MITF) in HPMs. In conclusion, this study identifies the presence of Th9 cells in vitiligo and their roles in reducing the oxidative stress of melanocytes, which might be useful in designing effective therapeutics.

中文翻译：

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IL-9/Th9 轴在白癜风中的存在和作用

免疫失调在白癜风发病机制中至关重要。尽管已经描述了许多 CD4 ⁺ T 细胞亚群的存在和作用，但尚未探索 Th9 细胞的存在，更重要的是，IL-9 对黑素细胞功能的作用。在这里，我们通过多色流式细胞术量化了白癜风患者的 T 辅助细胞亚群，包括 Th9 细胞。皮肤归巢 (CLA ⁺ ) 和全身 (CLA ^-）与健康供体相比，白癜风患者的 Th9 细胞。然而，早期和慢性白癜风患者的 Th9 细胞频率没有差异。人原代黑素细胞 (HPM) 上的 IL-9 受体 (IL-9R) 表达可忽略不计；然而，IFNγ 上调 HPM 上的 IL-9R 表达。在功能上，IL-9/IL-9R 信号传导减少了 HPM 中 IFNγ 诱导的毒性活性氧 (ROS) 的产生。IL-9 对负责黑素体形成（MART1、TYRP1和DCT）、黑色素合成（TYR）和黑素细胞诱导转录因子（MITF ）的基因的表达没有影响) 在 HPM 中。总之，这项研究确定了白癜风中 Th9 细胞的存在及其在减少黑素细胞氧化应激中的作用，这可能有助于设计有效的治疗方法。