Delayed type hypersensitivity reactions to various allergens may differently model inflammatory skin diseases.
allergic contact dermatitis
biomarker
contact dermatitis
inflammation
inflammatory skin disease
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
22
08
2022
received:
19
06
2022
accepted:
08
09
2022
pubmed:
1
10
2022
medline:
30
12
2022
entrez:
30
9
2022
Statut:
ppublish
Résumé
Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses. We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR. All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p < .05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL-1α, IL-8), Th1 (IFNγ, CXCL10), Th2 (IL-5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL-34, IL-37) (FDR <0.01). Nickel induced Th17 (IL-17A), Th1 (CXCL10) and Th2 (IL-4R) immune responses to a lesser extent than DPCP (p < .05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL-17A) (p < .05). DM induced modulation of Th2 (IL-13, CCL17, CCL18), Th22 (IL-22), and Th17/Th22 (S100A7/9/12) pathways (p < .05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)-related markers. Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis.
Sections du résumé
BACKGROUND
Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses.
METHODS
We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR.
RESULTS
All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p < .05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL-1α, IL-8), Th1 (IFNγ, CXCL10), Th2 (IL-5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL-34, IL-37) (FDR <0.01). Nickel induced Th17 (IL-17A), Th1 (CXCL10) and Th2 (IL-4R) immune responses to a lesser extent than DPCP (p < .05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL-17A) (p < .05). DM induced modulation of Th2 (IL-13, CCL17, CCL18), Th22 (IL-22), and Th17/Th22 (S100A7/9/12) pathways (p < .05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)-related markers.
CONCLUSION
Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis.
Substances chimiques
Allergens
0
Interleukin-17
0
Nickel
7OV03QG267
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
178-191Informations de copyright
© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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