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Shasha Jin,* Yixin Wang,* Chenxin Qie, Lu Yang, Yinhao Wu, Tingting Zhang, Jianwen Di, Jun Liu New Drug Screening Center, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Liu, New Drug Screening Center, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China, Tel +86-25-83271043, Fax +86-25-83271142, Email junliu@cpu.edu.cnPurpose: 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 mo