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

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.

Resveratrol Ameliorates Imiquimod-Induced Psoriasis-Like Mouse Model via Reducing Macrophage Infiltration and Inhibiting Glycolysis

“… 7 Recently, single-cell RNA sequencing revealed that macrophages were the main group of immune cells in IMQ-induced psoriasis mice. 25 Our study also found that the percentage of macrophages in skin lesions was prominently elevated, about 61.29%, which is similar to what was previously reported. The extensive infiltration of macrophages in psoriasis lesions deserves further investigation to elucidate the relationship between macrophage levels and activities and the pathogenesis of psoriasis.…”

The Efficacy of Imiquimod-Induced Psoriasis Model on Murine Cells

“…Across both tSNE and UMAP plots, cell types were more widespread in IMQ samples compared to control samples, revealing the diversity in heterogenous cell identity, which was also indicated by previous research [ 20 ] that used different gene markers for each cell type.…”

“…Across other studies, many different resolutions were used to identify cell cluster groups, with the most used being a 0.5 resolution [ 20 , 21 ]. However, when implementing a 0.5-resolution tSNE plot with the single-cell RNA sequencing data, too few cell clusters were identified as unique, resulting in the loss of many cell groups.…”

“…Second, different resolutions can be used to further categorize cell clusters in tSNE plots. Specifically, this data can be reevaluated using a 0.5 resolution, as done by previous research [ 20 , 21 ].…”

Single-cell RNA-seq reveals keratinocyte and fibroblast heterogeneity and their crosstalk via epithelial-mesenchymal transition in psoriasis

“…As an autoimmune disease, various cells, including KCs, FBs, pDCs, NKT cells, and macrophages, are involved in the entire immune process of psoriasis [ 3 , 4 ]. Jin et al used scRNA-seq to reveal the immune cell spectrum of IMQ-induced mice with psoriasis and observed that the proportions of macrophages, NK/T cells, cDCs and pDCs were increased in IMQ-treated mice compared with WT mice [ 27 ]. In our scRNA-seq analysis, the proportion of KCs and FBs showed the most significant difference, which indicated that KCs and FBs played important roles in the pathogenesis of psoriasis.…”