Non-IgE-reactive allergen peptides deteriorate the skin barrier in house dust mite-sensitized atopic dermatitis patients

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by type 2 cytokine-driven skin inflammation and epithelial barrier dysfunction. The latter is believed to allow the increased penetration of chemicals, toxins, and allergens into the skin. House dust mite allergens, particularly Der p 2, are important triggers in sensitized individuals with AD; the precise actions of these allergens in epithelial biology remain, however, incompletely understood. In this study, we compared the effects of the protein allergen Der p 2 and a mix of non-IgE-reactive Der p 2 peptides on skin cells using patch tests in AD patients and healthy participants. We then analyzed mRNA expression profiles of keratinocytes by single-cell RNA-sequencing. We report that existing barrier deficiencies in the non-lesional skin of AD patients allow deep penetration of Der p 2 and its peptides, leading to local microinflammation. Der p 2 protein specifically upregulated genes involved in the innate immune system, stress, and danger signals in suprabasal KC. Der p 2 peptides further downregulated skin barrier genes, in particular the expression of genes involved in cell–matrix and cell–cell adhesion. Peptides also induced genes involved in hyperproliferation and caused disturbances in keratinocyte differentiation. Furthermore, inflammasome-relevant genes and IL18 were overexpressed, while KRT1 was downregulated. Our data suggest that Der p 2 peptides contribute to AD initiation and exacerbation by augmenting hallmark features of AD, such as skin inflammation, barrier disruption, and hyperplasia of keratinocytes.

Stiffness-dependent LOX regulation via HIF-1 drives extracellular matrix modifications in psoriasis

“…GSE162183). Each sample underwent a quality control pipeline individually, before merging the datasets and analyzing them with Seurat [48] as described previously [49]. Microarray gene expression data from Yao et al .…”

“…GSE162183). Each sample underwent a quality control pipeline individually, before merging the datasets and analyzing them with Seurat [48] as described previously [49]. Microarray gene expression data from Yao et al comprising 80 healthy (H), lesional (L) and non-lesional (NL) psoriasis skin samples (Affymetrix Human Genome U133 Plus 2.0 Array, GSE14905 [19]) were analyzed using Genevestigator (Immunai/NEBION).…”