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

Behind Paper: The epidermal CD1c+CD11b+ cDC2s poised in the psoriasis perilesional skin, prepare the tissue and initiate inflammation,co-work with CD207+CD11chi LCs and CD5+ T cells in the psoriatic epidermis.
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The epidermal immune microenvironment plays a dominant role in psoriasis development, as revealed by mass cytometry

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. This study 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. Compared with that of the dermis, the epidermal immune environment was more significant and coincided with the inflammation occurring during psoriasis.

 

The key immune cells in psoriasis initiation and progression

The data showed the dramatic dynamics of epidermal DCs and LCs during psoriasis development. Psoriatic

dermal CD1c+CD11b+ cDC2s migrated to the epidermis in the perilesional skin, rapidly replacing EpCAM+CD11clow LCs to prepare the tissue and initiate inflammation. CD141+ cDC1s, CD1c+cDC2s,

CD14+ moDCs, and BDCA2+ pDCs orchestrated the psoriatic epidermal immune microenvironment. Simultaneously, CD207+CD11chi LCs were present in the psoriatic epidermis, while the total number of LCs was decreased significantly. CD207+CD11chi LCs have an increased capacity to produce IL-23. The source of the skin pathological cytokine IL-23 is important in the pathogenesis of psoriasis and its translation is relevant to

Treatment. Meanwhile, CD5+ T cells accumulated in the psoriatic epidermis. The immune cell pool in the psoriatic dermis primarily included DCs and T cells. Compared with that of the dermis, the epidermal immune environment was more significant and coincided with the inflammation occurring during psoriasis.

 

 

Methods

This study profiled the heterogeneity of immune cells, especially DCs and T cells in the epidermis and dermis of nonlesional (NL), perilesional (PL), lesional (L), and cured-lesional(CL) skin of psoriasis patients, by performing cytometry by time of flight (CyTOF) and multicolor flow cytometry. Flow cytometry staining and analysis, Immunofluorescence staining were used to

 

Conclusions

 

The dynamics of epidermal and dermal immune cells during the initiation, plaque progression and resolution phases of psoriasis were studied. The data highlight that the epidermal immune microenvironment plays a dominant role in the development of psoriasis.

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