Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune...

Area of Science:

• Immunology
• Dermatology
• Genomics

Background:

• Previous single-cell studies had limited resolution of inflammatory cells in human skin.
• Functional subsets of immune cells were difficult to identify due to their low abundance.

Purpose of the Study:

• To overcome limitations in analyzing skin immune cells.
• To apply single-cell transcriptomics to emigrating cells from psoriasis skin.
• To elucidate gene expression profiles of pathogenic and regulatory immune cells in psoriasis.

Main Methods:

• Harvested emigrating cells from human psoriasis and control skin without enzyme digestion or cell sorting.
• Utilized simultaneous single-cell RNA sequencing and flow cytometry.
• Applied unsupervised clustering to analyze cell populations.

Main Results:

• Identified diverse cell types including T cells, dendritic cells, and keratinocytes.
• Discovered distinct transcriptome profiles in cutaneous type 17 T cells based on cytokine expression (IL-17A/F, IFN-γ/IL-10).
• Characterized semimature dendritic cells as regulatory, noting a subset with pathogenic markers (IL-23A, IL-36G) in psoriasis.
• Observed potentially impaired CCL27-CCR10 interaction due to decreased CCL27 in basal keratinocytes.

Conclusions:

• Single-cell transcriptomics of emigrating skin cells is an innovative platform.
• This approach allows comparison of heterogeneous immune cells in inflammatory skin diseases.
• Provides novel insights into immune cell subsets in psoriasis.