近日，上海交通大学医学院王宏林、Florent Ginhoux等研究人员合作发现，角质形成细胞中过多的多胺生成促进银屑病中树突状细胞的自我RNA感应。相关论文于2020年6月17日在线发表在《免疫》杂志上。

研究人员发现，白细胞介素17（IL-17）下调了银屑病角质形成细胞中的蛋白磷酸酶6（PP6），导致转录因子C /EBP-β的磷酸化和激活，并随后产生了精氨酸酶1。

角质形成细胞中缺乏Pp6的小鼠易患银屑病样皮肤炎症。缺乏Pp6的角质形成细胞中精氨酸酶1的积累促使尿素循环产生多胺。多胺可保护银屑病角质形成细胞释放的自身RNA免受降解，并促进髓样树突状细胞对自身RNA的内吞作用，进而促进依赖toll样受体7（TLR7）的RNA感应和IL-6的产生。精氨酸酶抑制剂改善了银屑病的鼠类和非人类灵长类动物模型中的皮肤炎症。

这些研究结果表明，银屑病角质形成细胞中的尿素循环反应过度和过多的多胺生成会促进自我RNA感知，而角质形成细胞中PP6的失调是一个关键事件，它会放大银屑病的炎症回路。

据悉，银屑病是一种慢性炎性疾病，其病因是多因素的。细胞代谢对银屑病的作用尚不清楚。

附：英文原文

Title: Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Sensing by Dendritic Cells in Psoriasis

Author: Fangzhou Lou, Yang Sun, Zhenyao Xu, Liman Niu, Zhikai Wang, Siyu Deng, Zhaoyuan Liu, Hong Zhou, Jing Bai, Qianqian Yin, Xiaojie Cai, Libo Sun, Hong Wang, Qun Li, Zhouwei Wu, Xiang Chen, Jun Gu, Yu-Ling Shi, Wufan Tao, Florent Ginhoux, Honglin Wang

Issue&Volume: 2020-06-17

Abstract: Psoriasis is a chronic inflammatory disease whose etiology is multifactorial. Thecontributions of cellular metabolism to psoriasis are unclear. Here, we report thatinterleukin-17 (IL-17) downregulated Protein Phosphatase 6 (PP6) in psoriatic keratinocytes,causing phosphorylation and activation of the transcription factor C/EBP-β and subsequentgeneration of arginase-1. Mice lacking Pp6 in keratinocytes were predisposed to psoriasis-likeskin inflammation. Accumulation of arginase-1 in Pp6-deficient keratinocytes drovepolyamine production from the urea cycle. Polyamines protected self-RNA released bypsoriatic keratinocytes from degradation and facilitated the endocytosis of self-RNAby myeloid dendritic cells to promote toll-like receptor-7 (TLR7)-dependent RNA sensingand IL-6 production. An arginase inhibitor improved skin inflammation in murine andnon-human primate models of psoriasis. Our findings suggest that urea cycle hyperreactivityand excessive polyamine generation in psoriatic keratinocytes promote self-RNA sensationand PP6 deregulation in keratinocytes is a pivotal event that amplifies the inflammatorycircuits in psoriasis.

DOI: 10.1016/j.immuni.2020.06.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30234-X