调节性T细胞（Treg）功能缺陷导致毒性杀伤性T细胞（CTL）过度活化，是白癜风黑素细胞（MC）损伤的关键原因，但皮肤Treg在白癜风发病中的作用及调控机制均不清楚。我们最近发现白癜风皮肤组织中调控Treg迁移、抑制功能的关键基因CCL22、FOXP3、IL-2RA，以及调控Treg促MC再生功能的Jag-1甲基化水平升高，并初步证实上述异常表观修饰引起Treg功能受损，导致CTL过度活化、MC免疫损伤且再生障碍。基于前期研究及文献，我们提出科学假说：白癜风皮肤微环境及Treg细胞内特定基因甲基化改变，导致Treg皮肤迁移、免疫抑制及促MC再生功能障碍，介导白癜风发病。为证明该假说，我们拟结合临床样本及白癜风动物模型，系统鉴定皮肤Treg表型及特异表观修饰变化，揭示皮肤Treg区域免疫特性，阐明其在白癜风发病中的作用及表观遗传调控机制，结果有望发现白癜风靶向Treg的表观遗传干预治疗策略。

Vitiligo is characterized by epidermal melanocytes (MCs) loss due to regulatory T cells (Tregs)-mediated over activation of cytotoxic T lymphocytes (CTLs), but the molecular pathogenesis of skin Tregs remains largely unknown. We recently identified vitiligo-specific changes in some key genes including CCL22 that regulates the skin infiltration of Tregs, FOXP3 and IL-2RA that control the function of Tregs, as well as Jag-1 that mediates melanocyte regeneration by DNA methylation screening. And these epigenetics modifications lead to an impaired function of skin Tregs, which result in CTLs over activation, MCs autoimmune destruction and impaired MCs regeneration. Based on our latest findings and recent advancement in Tregs epigenetics, we hypothesize that DNA and/or histone methylation of specific genes in vitiligo skin will cause the migration and function defects of skin Tregs, and consequently leads to CTLs over activation, MCs destruction and MCs regeneration impairment. To test this hypothesis, we plan to identify the immune phenotype and epigenetics modifications of skin Tregs by analysis of patient-derived samples and mouse models, and then clarify the specific immune features in skin tissues and the elaborated mechanism of how epigenetic modification regulates Tregs functions in vitiligo. Our research will have important implications for rational clinical options.