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

• Published in: Allergy (Copenhagen) 2023-02, Vol.78 (2), p.439-453
• Main Authors: Zhang, Bowen, Roesner, Lennart M., Traidl, Stephan, Koeken, Valerie A. C. M., Xu, Cheng‐Jian, Werfel, Thomas, Li, Yang
• Format: Article
• Language: English
• Subjects: Antiviral drugs; Atopic dermatitis; Biopsy; Cell activation; Chronic Disease; chronic inflammatory diseases; Comparative analysis; Dermatitis; Dermatitis, Atopic; Disease; Eczema; Fibroblasts; Gene expression; Helper cells; Humans; Immunity; Inflammation; Inflammation - pathology; Inflammatory diseases; Keratinocytes; Lymphocytes T; Macrophages; Myeloid cells; Pericytes; Psoriasis; single‐cell immune profiling; Skin - pathology; Skin diseases; Skin Diseases - pathology; Stromal cells; T cell receptors; type‐2 immunity; type‐3 immunity
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.15486

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. We applied single‐cell RNA and TCR sequencing on immune‐cells enriched from skin biopsies and matched blood samples of atopic dermatitis and psoriasis patients. We uncovered disease specific Th2/Th22 and Th17/Tc17 sub‐populations in atopic dermatitis and psoriasis, respectively, and associated their numbers with severity scores in both diseases. The disease specific signatures contributed to the hallmarks of type‐2 and type‐3 inflammatory signatures and were associated with disease activitiesAbbreviations: DC, dendritic cell; TCR, T‐cell receptor; Th, T‐helper cell; Tc17, T‐cytotoxic 17 cell