The Single-Cell Atlas Reveals Subset-Specific Transcriptional Programs of NK Cells in Skin Inflammation

Natural killer (NK) cells are crucial in inflammatory skin diseases, but their diverse functions and lack of a standardized classification system across diseases have limited deeper insights into their roles.

We merged single-cell transcriptomic data from 40 skin samples to create a comprehensive atlas of NK cells across various skin diseases, identifying nine distinct NK cell subsets with unique functions.

Our analysis revealed a conserved Aryl Hydrocarbon Receptor (AHR)⁺ NK cell subset that is broadly present across multiple skin diseases. Notably, the Granzyme B (GZMB)⁺ NK cell subset may be associated with the pathogenesis of psoriasis (PSO) and appears to undergo a differentiation trajectory toward IL13⁺ NK cells in the pseudotime analysis. This finding suggests a potential role for these cells in mediating paradoxical cutaneous inflammation. Our analysis identified NK cells expressing GZMB in a variety of skin diseases. Notably, the NK cell subpopulation expressing GZMB appears to be associated with the pathogenesis of PSO and ultimately exhibits the expression of IL13 in pseudotime analysis, suggesting that it may play a role in regulating contradictory skin inflammation.

This study offers a comprehensive overview of skin NK cells, identifies pathogenic subsets that may drive skin disease progression, and provides novel insights for future targeted therapies.