Understanding psoriatic disease at single-cell resolution: an update.

Area of Science:

• Dermatology and immunology
• Genomics and transcriptomics
• Systems biology

Background:

• Psoriasis is a complex, heterogeneous inflammatory skin disease.
• Understanding the cellular and molecular drivers of psoriasis is crucial for developing effective treatments.

Purpose of the Study:

• To review advancements in psoriasis research using single-cell technologies.
• To elucidate the cellular diversity and key pathways involved in psoriasis pathogenesis.
• To identify potential targets for precision therapies.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq)
• Spatial transcriptomics
• Analysis of immune cell, keratinocyte, and fibroblast subtypes

Main Results:

• Identified key roles for IL-17-producing T cells, keratinocytes, and fibroblasts in psoriasis inflammation.
• Revealed fibroblast-keratinocyte crosstalk via IL-17/IL-36 and PRSS3-F2R pathways.
• Uncovered metabolic dysregulation (HIF1α-driven glycolysis) in psoriatic keratinocytes and systemic prelesional transcriptomic changes.

Conclusions:

• Single-cell and spatial technologies offer new insights into psoriasis heterogeneity.
• Potential for developing targeted therapies by addressing metabolic pathways and immune microenvironments.
• Spatial transcriptomics may identify early indicators of disease severity and systemic involvement.