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单细胞RNA测序揭示咪喹莫特诱导的银屑病样模型中的免疫细胞图谱。

Single-Cell RNA Sequencing Reveals the Immune Cell Profiling in IMQ Induced Psoriasis-Like Model.

作者信息

Jin Shasha, Wang Yixin, Qie Chenxin, Yang Lu, Wu Yinhao, Zhang Tingting, Di Jianwen, Liu Jun

机构信息

New Drug Screening Center, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.

出版信息

J Inflamm Res. 2022 Oct 28;15:5999-6012. doi: 10.2147/JIR.S379349. eCollection 2022.

Abstract

PURPOSE

Psoriasis is a chronic systemic inflammatory skin disease with a high recurrence rate. The immune response plays an important role in psoriasis. However, the subsets of immune cells involved in inflammation in psoriatic mice have not been fully studied. This study showed the immune environment characteristics of psoriasis in mice.

METHODS

We used single-cell RNA sequencing (10× Genomics) as an unbiased analytical strategy to investigate the heterogeneity of skin immune cells in imiquimod-induced psoriasis mice systematically.

RESULTS

We identified 10 major clusters and their marker genes among 14,439 cells. The proportions of macrophages, NK/T cells, conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) were increased in psoriatic mice. Macrophages were the largest group and were further divided into 7 subgroups, and all macrophage clusters were increased in psoriatic mice. Differentially expressed genes in control versus psoriatic mice skin lesions showed that Fcgr4, Saa3 and Acp5 in macrophages, Acp5, Fcgr4 and Ms4a6d in NK/T cells, Saa3 in cDCs, and Ifitm1 in pDCs were upregulated in psoriasis mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis emphasized the role of oxidative phosphorylation signals and antigen processing and presentation signals in murine psoriasis-like models.

CONCLUSION

Our study reveals the immune environment characteristics of the commonly used IMQ induced psoriasis-like models and provides a systematic insight into the immune response of mice with psoriasis, which is conducive to comparing the similarities and differences between the mouse model and human psoriasis.

摘要

目的

银屑病是一种慢性全身性炎症性皮肤病,复发率高。免疫反应在银屑病中起重要作用。然而,参与银屑病小鼠炎症的免疫细胞亚群尚未得到充分研究。本研究展示了小鼠银屑病的免疫环境特征。

方法

我们使用单细胞RNA测序(10×基因组学)作为一种无偏分析策略,系统地研究咪喹莫特诱导的银屑病小鼠皮肤免疫细胞的异质性。

结果

我们在14439个细胞中鉴定出10个主要细胞簇及其标记基因。银屑病小鼠中巨噬细胞、NK/T细胞、传统树突状细胞(cDCs)和浆细胞样树突状细胞(pDCs)的比例增加。巨噬细胞是最大的群体,进一步分为7个亚组,所有巨噬细胞簇在银屑病小鼠中均增加。对照小鼠与银屑病小鼠皮肤病变中的差异表达基因显示,巨噬细胞中的Fcgr4、Saa3和Acp5,NK/T细胞中的Acp5、Fcgr4和Ms4a6d,cDCs中的Saa3,以及pDCs中的Ifitm1在银屑病小鼠中上调。京都基因与基因组百科全书(KEGG)信号通路富集分析强调了氧化磷酸化信号和抗原加工与呈递信号在小鼠银屑病样模型中的作用。

结论

我们的研究揭示了常用的咪喹莫特诱导的银屑病样模型的免疫环境特征,并为银屑病小鼠的免疫反应提供了系统的见解,这有助于比较小鼠模型与人类银屑病之间的异同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8392/9626250/fdd54048beef/JIR-15-5999-g0001.jpg

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