关键词: Dendritic cell Halo nevus Metabolite Spatial transcriptomics Uridine diphosphate glucose (UDP-G) Vitiligo

来  源:   DOI:10.1016/j.clim.2024.110300

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综合分析,以更好地了解晕痣的进展。我们发现晕痣的特点是免疫反应过度活跃,由趋化因子和树突状细胞(DC)触发,T细胞,和巨噬细胞。因此,我们观察到细胞异常死亡,如晕痣的细胞凋亡和二硫化物沉积,有些与免疫力密切相关。有趣的是,我们鉴定了晕痣内的异常代谢物,例如尿苷二磷酸葡萄糖(UDP-G)。UDP-G,伴随着DC和T细胞的浸润,表现出与某些形式的细胞死亡的相关性。随后的实验证实,白癜风血清中UDP-G增加,并可以激活DC。我们还证实了氧化反应是UDP-G的诱导剂。总之,晕痣的免疫反应,包括DC激活,伴随着异常的细胞死亡和代谢产物。尤其是,黑素细胞来源的UDP-G可能在DC激活中起关键作用。
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