Miao Fang, Li Xiaohui, Zhao Liang, Zhang Shijiao, Geng Mengmeng, Ye Chuhuan, Shi Ying, Lei Tiechi
Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Int J Mol Sci. 2025 Jul 15;26(14):6787. doi: 10.3390/ijms26146787.
Autoimmune CD8 T cell-driven melanocyte destruction constitutes a key pathogenic mechanism in the development of vitiligo. Therefore, the pharmacological inhibition of CD8 T cell effector functions and skin trafficking is a clinically viable therapeutic strategy. This study investigates leflunomide (LEF), an immunomodulatory drug with established safety in autoimmune diseases, for its therapeutic potential in a tyrosine-related protein (TRP) 2-180-induced vitiligo mouse model. Through flow cytometry, immunofluorescence, ELISA, and histopathological analyses, we systematically evaluated LEF's effects on T cell regulation, chemokine expression, and cytokine profiles. Key findings demonstrated that LEF (20 mg/kg/day) significantly attenuated depigmentation by reducing CD8 T cell infiltration and suppressing the IFN-γ-driven expression of CXCL9/10. Furthermore, LEF restored CD4/CD8 T cell homeostasis and rebalanced pro-inflammatory (IFN-γ, TNF-α, IL-2) and anti-inflammatory (IL-4, IL-10) cytokines, inducing a shift from Th1 to Th2. These results position LEF as an effective immunomodulator that disrupts the IFN-γ-CXCL9/10 axis and re-establishes immune balance, offering a promising repurposing strategy for halting vitiligo progression.
自身免疫性CD8 T细胞驱动的黑素细胞破坏是白癜风发病的关键致病机制。因此，药理学抑制CD8 T细胞效应功能和皮肤迁移是一种临床上可行的治疗策略。本研究调查了来氟米特（LEF），一种在自身免疫性疾病中具有既定安全性的免疫调节药物，在酪氨酸相关蛋白（TRP）2 - 180诱导的白癜风小鼠模型中的治疗潜力。通过流式细胞术、免疫荧光、酶联免疫吸附测定和组织病理学分析，我们系统地评估了LEF对T细胞调节、趋化因子表达和细胞因子谱的影响。主要研究结果表明，LEF（20毫克/千克/天）通过减少CD8 T细胞浸润和抑制IFN - γ驱动的CXCL9/10表达，显著减轻色素脱失。此外，LEF恢复了CD4/CD8 T细胞稳态，并重新平衡了促炎（IFN - γ、TNF - α、IL - 2）和抗炎（IL - 4、IL - 10）细胞因子，诱导了从Th1到Th2的转变。这些结果表明LEF是一种有效的免疫调节剂，可破坏IFN - γ - CXCL9/10轴并重新建立免疫平衡，为阻止白癜风进展提供了一种有前景的重新利用策略。
