Delayed type hypersensitivity reactions to various allergens may differently model inflammatory skin diseases

Ana B. Pavel, Ester Del Duca, Julia Cheng, Jianni Wu, Benjamin Ungar, Yeriel D. Estrada, Carolyn Jack, Catherine Maari, Étienne Saint Cyr Proulx, Francisco Ramirez-Valle, James G. Krueger, Robert Bissonnette, Emma Guttman-Yassky

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)178-191
Number of pages14
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume78
Issue number1
DOIs
StatePublished - Jan 2023

Keywords

  • allergic contact dermatitis
  • biomarker
  • contact dermatitis
  • inflammation
  • inflammatory skin disease

Fingerprint

Dive into the research topics of 'Delayed type hypersensitivity reactions to various allergens may differently model inflammatory skin diseases'. Together they form a unique fingerprint.

Cite this