氧化应激启动异常免疫应答是白癜风近年研究热点之一。申请者既往研究发现， 氧化应激诱导CRT膜聚集及gC1qR线粒体转位，促进TNF-α等细胞因子分泌，参与细胞凋亡、CTL增殖分泌及DC成熟，证实CRT/gC1qR在氧化应激-免疫应答中具有重要意义。程序性坏死是细胞凋亡失效时的“自动防故障机制”，与肿瘤及炎症密切相关。预实验发现白癜风皮损表达程序性坏死效应分子p-MLKL，提示程序性坏死可能参与发病，但是否与氧化应激共同作用促进黑素细胞破坏尚不得知。为阐明CRT/gC1qR在氧化应激诱导黑素细胞程序性坏死中的作用，拟利用氧化应激细胞模型深入分析凋亡与程序性坏死在白癜风黑素细胞破坏中的具体作用，明确膜型CRT及线粒体gC1qR对RIP1/RIP3/MLKL轴的调控机制，确定程序性坏死对表皮异常免疫应答的影响，探寻基于程序性坏死的新型治疗靶点，为全面认知白癜风发病机制，改进防治策略提供重要依据。

Oxidative stress initiating abnormal immune response is one of the research hotspots of vitiligo. Our previous findings suggested that oxidative stress could induce CRT membrane aggregation and gC1qR mitochondrial translocation, which promoted the secretion of cytokines including IL-6 and TNF-α, melanocyte apoptosis, CTL proliferation and DC maturation. It is confirmed that oxidative stress-related proteins have important significance on vitiligo pathogenesis due to cell surface and internal organelles translocation. Necroptosis is the “automatic fail-safe mechanism-" when apoptosis fails. It is closely related to tumors and chronic inflammatory diseases. We found that vitiligo skin lesions expressed necroptosis effector molecules (p-MLKL), suggesting that necroptosis might be involved in the pathogenesis of vitiligo. However, it is unknown whether oxidative stress interacts with necroptosis to promote melanocyte death. To elucidate the role of CRT/gC1qR in oxidative stress-induced melanocyte necroptosis, we plan to analyze the different roles of apoptosis and necroptosis in the destruction of vitiligo melanocytes, then find the regulation of ecto-CRT/mitochondrial gC1qR on RIP1/RIP3/MLKL axis, further confirm the effect of necroptosis on abnormal immune response and inflammatory in epidermis, then find some new therapeutic targets based on necroptosis. With the above researches, we may provide an important basis for comprehensively understanding of vitiligo pathogenesis and improving prevention strategies.