A scRNA-seq atlas of chronic inflammatory skin diseases

Abstract

Inflammatory skin diseases (ISDs) affect up to 25% of the global population. Yet, large-scale comparative single-cell RNA-sequencing (scRNA-seq) analyses between ISDs are still missing. Here, we integrated scRNA-seq datasets spanning 27 skin diseases from 50 studies, comprising over 2 million cells from 441 samples. Using the healthy skin cell atlas as reference, we could build a robust ISD atlas that enabled us to differentiate universal inflammatory signatures and disease-specific ones. This highlighted, for example, a shared gene program between keratinocytes in atopic dermatitis and parapsoriasis, not present in cutaneous T-cell lymphoma, confirms the plasticity of Th17 cells throughout ISDs, defines specific macrophage signatures in acne, and reveals a yet undescribed role of mural cells in ISDs. This demonstrates the power of the ISD atlas as a resource to resolve disease-specific immune mechanisms. The complete atlas is available through an interactive online portal at https://isd-atlas.derma.meduniwien.ac.at.