Enhanced Expression of Genes Related to Xenobiotic Metabolism in the Skin of Patients with Atopic Dermatitis but Not with Ichthyosis Vulgaris

Abstract

Previous transcriptome analyses underscored the importance of immunological and skin barrier abnormalities in atopic dermatitis (AD). We sought to identify pathogenic pathways involved in AD by comparing the transcriptomes of AD patients stratified for filaggrin (FLG)-null mutations to those of both healthy donors and patients with ichthyosis vulgaris. We applied RNA sequencing to analyze the whole transcriptome of nonlesional skin. We found that 607 genes (476 up-regulated and 131 down-regulated by >2-fold) and 193 genes (172 up-regulated and 21 down-regulated by >2-fold) were differentially expressed when all AD or ichthyosis vulgaris patients were compared with healthy donors, respectively. Expression of genes involved in RNA/protein turnover and adenosine triphosphate synthesis, as well as genes involved in cell death, response to oxidative stress, DNA damage/repair, and autophagy, were significantly enriched in AD skin and, to a lesser extent, in ichthyosis vulgaris skin. FLG-null mutations appear to hardly interfere with current observations. Genes related to xenobiotic metabolism were up-regulated in AD skin only, as were genes related to arachidonic, linoleic, and α-linolenic acid metabolism. Thus, this work newly links AD pathogenesis to aberrant expression of genes related to xenobiotic metabolism.

Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis

“…Tregs exposed to phenanthrene show decreased TGF‐β and IL‐10 and increased IL‐4, IL‐13, (p)STAT6 and GATA‐3 . It has recently been shown that repeated exposure to air pollution and to noxious molecules may promote AD . Thus, pollutants may contribute to AD also via their ability to affect Treg populations, especially by impeding their immunosuppressive capacity by causing them to redifferentiate into Th‐like cells that produce proinflammatory cytokines.…”

“…Worldwide, AD prevalence is relatively high, affecting 15%‐30% of children and 2%‐10% of adults. Notably, AD prevalence has markedly increased during the past 40 years, potentially because of a higher pollution burden …”

“…Notably, AD prevalence has markedly increased during the past 40 years, potentially because of a higher pollution burden. [1][2][3][4] The pathogenesis of AD is complex and not yet fully understood.…”

“…Notably, AD prevalence has markedly increased during the past 40 years, potentially because of a higher pollution burden. [1][2][3][4] The pathogenesis of AD is complex and not yet fully understood.Epidermal barrier defects and immune hyper-responsiveness are the main features of AD. Meta-analysis of genome-wide association studies identified a risk locus in the epidermal differentiation complex and especially the filaggrin (FLG) gene.…”

ÖGDV Preisträger stellen sich vor: Der Österreichische Dermatologenpreis – Unilever Preis 2017 ging an Dr. Stefan Blunder aus Innsbruck

“…Das Ziel der prämierten Arbeit war es, die molekulare Signatur der Haut von Patienten mit Atopischer Dermatitis mit und ohne Filaggrin Mutation sowie Ichthyosis vulgaris zu entschlüsseln, um somit die Rolle von Filaggrin in der Entstehung der Atopischen Dermatitis versus Ichthyosis vulgaris genauer definieren zu können. Zu diesem Zweck verwendeten die Autoren „Next Generation Sequencing“ um die Transkriptome von Hautproben von Kontrollpersonen und Patienten mit (i) Atopischer Dermatitis ohne Filaggrin Mutationen, (ii) Atopischer Dermatitis mit Filaggrin Mutationen, (iii) Ichthyosis Vulgaris sowie von Patienten mit (iiii) Ichthyosis Vulgaris und Atopischer Dermatitis zu vergleichen . Dabei wurde die überraschende Entdeckung gemacht, dass in der Atopischen Dermatitis – unabhängig vom Filaggrin Mutationsstatus – Gene, welche im Metabolismus von Xenobiotika eine entscheidende Rolle spielen, verstärkt exprimiert werden.…”