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

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          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.

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          Most cited references54

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          Pathogenesis and therapy of psoriasis.

          Psoriasis is one of the most common human skin diseases and is considered to have key genetic underpinnings. It is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells, dendritic cells and various immune-related cytokines and chemokines implicated in pathogenesis. The newest therapies for psoriasis target its immune components and may predict potential treatments for other inflammatory human diseases.
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            Skin immune sentinels in health and disease.

            Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.
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              Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis.

              Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4(+) T cells, CD11c(+) dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis.
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                Author and article information

                Journal
                J Inflamm Res
                J Inflamm Res
                jir
                Journal of Inflammation Research
                Dove
                1178-7031
                28 October 2022
                2022
                : 15
                : 5999-6012
                Affiliations
                [1 ]New Drug Screening Center, Institute of Pharmaceutical Sciences, China Pharmaceutical University , Nanjing, 210009, People’s Republic of China
                Author notes
                Correspondence: 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.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-5129-8757
                Article
                379349
                10.2147/JIR.S379349
                9626250
                36330167
                636f3043-fd58-4536-bb43-316b2e22bf6b
                © 2022 Jin et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 02 July 2022
                : 20 October 2022
                Page count
                Figures: 6, References: 54, Pages: 14
                Funding
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: Natural Science Foundation of Jiangsu Province, open-funder-registry 10.13039/501100004608;
                This work was supported by the National Natural Science Foundation of China (No. 81973361) and Natural Science Foundation of Jiangsu Province (BK20202009).
                Categories
                Original Research

                Immunology
                single-cell rna sequencing,psoriasis,imiquimod,immune cells
                Immunology
                single-cell rna sequencing, psoriasis, imiquimod, immune cells

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