白癜风黑素细胞凋亡小体形成及其抗原呈递机制的研究

白癜风发病与自身免疫密切相关。研究证明，黑素细胞抗氧化功能缺陷、高氧化应激诱导细胞凋亡进而启动抗原特异性免疫应答，是发病过程中的重要环节。但凋亡后自身抗原如何暴露的分子机制尚不清楚。我们前期发现：核纤层蛋白Lamin A是一种新的白癜风抗原，在氧化应激诱导的黑素细胞凋亡早期，与酪氨酸酶等抗原共同形成凋亡小体（AB），而AB是自身免疫疾病T、B细胞抗原产生的重要来源，这为抗原暴露的研究提供重要线索。因此本项目拟运用电镜、免疫印迹等手段，以白癜风黑素细胞AB为主要研究对象，检测分析在氧化应激诱导凋亡早期、晚期，启动凋亡、形成AB的信号通路，AB蛋白组成及抗原再定位机制，胞内、外危险信号的促吞噬功能，在动物水平验证AB免疫应答的特异性，深入阐释AB形成、免疫识别及吞噬的一系列分子事件。最终阐明AB介导的免疫呈递机制。结果有望揭示白癜风细胞凋亡与免疫应答间的内在联系，进一步完善白癜风的发病机制。

A number of studies suggest that vitiligo is a common autoimmune disease. Loss of epidermal melanocytes is induced by abnormal immune reactions triggered by the excessive oxidative stress. However, the presenting process of the autoantigen remains unknown in apoptotic vitiligo melanocytes. We found that the autoantigens can be relocated into apoptotic bodies, which is key resource of T and B cell epitopes. It suggested an important clue for search into the antigen presentation. Thus, we are planning to use flow cytometry, light microscope, western blotting, laser confocal fluorescence microscope and animal investigations to identify whether apoptotic bodies that contain translocated lamin A and other autoantigens are involved in the presentation of autoantigens from melanocytes under the excessive oxidative stress. The project will be useful for disclosing the correlationship among oxidative stress, melanocyte apoptosis and immune response, and it can further enhance the full understanding of vitiligo pathogenesis.