Single-cell profiles reveal distinctive immune response in atopic dermatitis in contrast to psoriasis

Background Understanding the complex orchestrated inflammation in atopic dermatitis (AD), one of the most common chronic inflammatory diseases worldwide, is essential for therapeutic approaches. However, a comparative analysis on the single-cell level of the inflammation signatures correlated with the severity is missing so far. Methods We applied single-cell RNA and T-cell receptor (TCR) sequencing on immune cells enriched from skin biopsies and matched blood samples of AD in comparison with psoriasis (PS) patients. Results Clonally propagated skin-derived T cells showed disease-specific TCR motifs shared between patients which was more pronounced in PS compared to AD. The disease-specific T-cell clusters were mostly of a Th2/Th22 sub-population in AD and Th17/Tc17 in PS, and their numbers were associated with severity scores in both diseases. Herein, we provide for the first time a list that associates cell type-specific gene expression with the severity of the two most common chronic inflammatory skin diseases. Investigating the cell signatures in the patients ' PBMCs and skin stromal cells, a systemic involvement of type-3 inflammation was clearly detectable in PS circulating cells, while in AD inflammatory signatures were most pronounced in fibroblasts, pericytes, and keratinocytes. Compositional and functional analyses of myeloid cells revealed the activation of antiviral responses in macrophages in association with disease severity in both diseases. Conclusion Different disease-driving cell types and subtypes which contribute to the hallmarks of type-2 and type-3 inflammatory signatures and are associated with disease activities could be identified by single-cell RNA-seq and TCR-seq in AD and PS.

Automated summary

Single-cell analysis of atopic dermatitis and psoriasis patients revealed disease-specific T cell clusters and identified cell type-specific gene expression associated with inflammation signatures and disease severity. The study shed light on the complexity of inflammatory responses and provided valuable insights for further investigation and therapeutic approaches for these chronic inflammatory skin diseases.