Single-cell profiles reveal distinctive immune response in atopic dermatitis in contrast to psoriasis.
atopic dermatitis
chronic inflammatory diseases
single-cell immune profiling
type-2 immunity
type-3 immunity
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
21
06
2022
received:
02
02
2022
accepted:
18
07
2022
pubmed:
21
8
2022
medline:
1
2
2023
entrez:
20
8
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
439-453Informations de copyright
© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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