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The epidermal immune microenvironment plays a dominant role in psoriasis development, as revealed by mass cytometry

Cellular & Molecular Immunology volume 19, pages 1400–1413 (2022)Cite this article

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Abstract

Psoriasis is a common chronic inflammatory skin disease. The diversity and heterogeneity of immune cells in human skin have been studied in recent years, but the spatial distribution of immune cells at the single-cell level in the human psoriatic epidermis and dermis remains unclear. In this study, we mapped psoriatic skin immune cells from paired lesional, perilesional, and nonlesional skin samples using mass cytometry. Phenotypic dendritic cells (DCs) were found in the psoriatic epidermis and dermis. Psoriatic dermal CD1c+CD11b+ cDC2s migrated to the epidermis in the perilesional skin during the preinitiation stage. CD1c+CD11b+ cDC2s rapidly replaced EpCAM+CD11clow LC cells and initiated inflammation. Simultaneously, CD207+CD11chi LC and CD5+ T cells accumulated in the psoriatic epidermis and orchestrated epidermal inflammation in psoriasis. The immune cell pool in the psoriatic dermis primarily included APCs and T cells. However, unlike that in the dermis, the epidermal immune environment was more significant and coincided with the inflammation occurring during psoriasis.

The epidermal immune microenvironment plays a dominant role in psoriasis. Langerhans cells, epidermis-resident memory T cells and macrophages together contribute to healthy epidermal immune homeostasis. However, psoriatic CD1c+CD11b+ epidermal cDC2s are positioned in the perilesional area, replacing EpCAM+CD11clow LCs rapidly and initiating inflammation. Epidermal CD141+ cDC1s, CD1c+ cDC2s, CD14+ moDCs, and BDCA2+ pDCs orchestrate psoriatic inflammation. Meanwhile, CD11chi LCs and CD5+ T cells accumulate in the psoriatic epidermis

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (No. 81930089, 82103709, and 82230104). The authors wish to thank PLTTECH (ZJ, China) for providing technical support and kind assistance with the mass cytometry analysis. The authors wish to thank Prof. Qing-Sheng Mi for providing kind advice on this project.

Funding

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81930089, 82103709, and 82230104).

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  1. These authors contributed equally: Yuan Zhou, Fan Xu, Xue-Yan Chen.

Authors and Affiliations

  1. Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Yuan Zhou, Fan Xu, Xue-Yan Chen, Bing-Xi Yan, Zhao-Yuan Wang, Si-Qi Chen, Min Zheng & Xiao-Yong Man

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Contributions

MZ and XYM designed the research studies; XYM and MZ supervised the methods and administered and funded the project; YZ, FX and XYC conducted the experiments; YZ and FX acquired the data and analyzed the data; BXY, ZYW and SQC provided reagents; YZ wrote the manuscript; and FX and XYM edited the paper. YZ, FX and XYC conducted experiments including processing samples and performing CyTOF staining and flow cytometry, and YZ refined concepts and wrote the manuscript; these three authors contributed equally to this work.

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Correspondence to Xiao-Yong Man.

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The study was approved by the Ethics Committee of the Second Affiliated Hospital, Zhejiang University School of Medicine.

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Zhou, Y., Xu, F., Chen, XY. et al. The epidermal immune microenvironment plays a dominant role in psoriasis development, as revealed by mass cytometry. Cell Mol Immunol 19, 1400–1413 (2022). https://doi.org/10.1038/s41423-022-00940-8

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