Rationale: V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule. Vsir^-/- mice have exacerbated psoriasis-like skin inflammation. The immune cell subsets involved in inflammation in Vsir^-/- psoriatic mice are largely unknown. We have used scRNA-seq as an unbiased profiling strategy to study the heterogeneity of immune cells at a single cell level in the skin of Vsir^-/- psoriatic mice./nMethods: In the present study, the right ear and shaved back skin of wild type and Vsir^-/- mice were treated with IMQ for 5 consecutive days to induce psoriasis-like dermatitis. Then, the single-cell RNA sequencing analysis of mouse back skin lesions was performed using 10 × Genomics technique./nResults: We identified 12 major cell subtypes among 23,258 cells. The major populations of the skin cells included macrophages, dendritic cells and fibroblasts. Macrophages constituted the main immune cell population in the WT (61.29%) and Vsir^-/- groups (77.7%). It should be noted that DCs and fibroblasts were expanded in the Vsir^-/- psoriatic mice. Furthermore, the gene expression signatures were assessed. We observed that Hspb1 and Cebpb were significantly upregulated in the Vsir^-/- psoriatic mice. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these subsets and uncovered putative functions of each cell type. Date analysis resulted in the discovery of a number of novel psoriasis-associated genes in Vsir^-/- mice./nConclusion: We present a comprehensive single-cell landscape of the skin immune cells in Vsir^-/- psoriatic mice. These unprecedented data uncovered the transcriptional landscape and phenotypic heterogeneity of skin macrophages in psoriasis and identified their gene expression signature suggesting specialized functions in Vsir^-/- mice. Our findings will open novel opportunities to investigate the role of VISTA in driving psoriasis.

中文翻译：

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单细胞RNA-Seq揭示了Vsir-/-鼠牛皮癣中皮肤巨噬细胞的转录情况和异质性。

原理： T细胞活化的V区免疫球蛋白抑制剂（VISTA）是一种新型的抑制性免疫检查点分子。Vsir ^-/-小鼠加剧了牛皮癣样皮肤炎症。Vsir ^-/-银屑病小鼠炎症中涉及的免疫细胞亚群基本上是未知的。我们已经使用scRNA-seq作为无偏倚的分析策略来研究Vsir ^-/-银屑病小鼠皮肤中单个细胞水平上免疫细胞的异质性。/n方法：在本研究中，右耳和剃毛的皮肤和Vsir的类型^-/-连续5天用IMQ治疗小鼠，以诱发牛皮癣样皮炎。然后，使用10×Genomics技术对小鼠背部皮肤病变进行单细胞RNA测序分析。/n结果：我们在23,258个细胞中鉴定出12种主要的亚型。皮肤细胞的主要种群包括巨噬细胞，树突状细胞和成纤维细胞。巨噬细胞构成了WT（61.29％）和Vsir ^-/-组（77.7％）的主要免疫细胞群。应当指出，DC和成纤维细胞在Vsir ^-/-银屑病小鼠中扩增。此外，评估了基因表达特征。我们观察到Hspb1和Cebpb在Vsir中显着上调^-/-银屑病小鼠。差异基因表达和基因本体论富集分析揭示了区分这些子集的特定基因表达模式，并揭示了每种细胞类型的推定功能。日期分析导致在Vsir ^-/-小鼠中发现了许多与牛皮癣相关的新基因。/n结论：我们提出了Vsir ^-/-银屑病小鼠皮肤免疫细胞的全面单细胞图谱。这些空前的数据揭示了牛皮癣皮肤巨噬细胞的转录景观和表型异质性，并确定了它们的基因表达特征，暗示了Vsir的特殊功能^-/-老鼠。我们的发现将为调查VISTA在驱动牛皮癣中的作用提供新的机会。