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黑素细胞的异常代谢参与晕痣中树突状细胞的活化。

Abnormal metabolism in melanocytes participates in the activation of dendritic cell in halo nevus.

机构信息

Department of Dermatology, The Third Xiangya Hospital, Central South University, No.138 Tongzipo Road, Changsha, Hunan 410013, PR China.

Clinical Research Center, The Second Xiangya Hospital, Central South University, No.139 Renmin Road, Changsha, Hunan 410011, PR China.

出版信息

Clin Immunol. 2024 Aug;265:110300. doi: 10.1016/j.clim.2024.110300. Epub 2024 Jun 29.

Abstract

A comprehensive analysis of spatial transcriptomics was carried out to better understand the progress of halo nevus. We found that halo nevus was characterized by overactive immune responses, triggered by chemokines and dendritic cells (DCs), T cells, and macrophages. Consequently, we observed abnormal cell death, such as apoptosis and disulfidptosis in halo nevus, some were closely related to immunity. Interestingly, we identified aberrant metabolites such as uridine diphosphate glucose (UDP-G) within the halo nevus. UDP-G, accompanied by the infiltration of DCs and T cells, exhibited correlations with certain forms of cell death. Subsequent experiments confirmed that UDP-G was increased in vitiligo serum and could activate DCs. We also confirmed that oxidative response is an inducer of UDP-G. In summary, the immune response in halo nevus, including DC activation, was accompanied by abnormal cell death and metabolites. Especially, melanocyte-derived UDP-G may play a crucial role in DC activation.

摘要

对空间转录组学进行了全面分析,以更好地了解晕痣的进展。我们发现晕痣的特征是免疫反应过度活跃,由趋化因子和树突状细胞(DC)、T 细胞和巨噬细胞引发。因此,我们观察到晕痣中存在异常细胞死亡,如凋亡和二硫键化,其中一些与免疫密切相关。有趣的是,我们在晕痣中鉴定出异常代谢物,如尿苷二磷酸葡萄糖(UDP-G)。UDP-G 伴随着 DC 和 T 细胞的浸润,与某些形式的细胞死亡相关。随后的实验证实,UDP-G 在白癜风血清中增加,并能激活 DC。我们还证实,氧化反应是 UDP-G 的诱导剂。总之,晕痣中的免疫反应包括 DC 激活,伴随着异常的细胞死亡和代谢物。特别是,黑素细胞衍生的 UDP-G 可能在 DC 激活中发挥关键作用。

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