Targeting the Cutaneous Microbiota in Atopic Dermatitis by Coal Tar via AHR-Dependent Induction of Antimicrobial Peptides.
J Invest Dermatol
; 140(2): 415-424.e10, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31344386
ABSTRACT
Skin colonization by Staphylococcus aureus and its relative abundance is associated with atopic dermatitis (AD) disease severity and treatment response. Low levels of antimicrobial peptides in AD skin may be related to the microbial dysbiosis. Therapeutic targeting of the skin microbiome and antimicrobial peptide expression can, therefore, restore skin homeostasis and combat AD. In this study, we analyzed the cutaneous microbiome composition in 7 patients with AD and 10 healthy volunteers upon topical coal tar or vehicle treatment. We implemented and validated a Staphylococcus-specific single-locus sequence typing approach combined with classic 16S ribosomal RNA marker gene sequencing to study the bacterial composition. During coal tar treatment, Staphylococcus abundance decreased, and Propionibacterium abundance increased, suggesting a shift of the microbiota composition toward that of healthy controls. We, furthermore, identified a hitherto unknown therapeutic mode of action of coal tar, namely the induction of keratinocyte-derived antimicrobial peptides via activation of the aryl hydrocarbon receptor. Restoring antimicrobial peptide levels in AD skin via aryl hydrocarbon receptor-dependent transcription regulation can be beneficial by creating a (anti)microbial milieu that is less prone to infection and inflammation. This underscores the importance of coal tar in the therapeutic aryl hydrocarbon receptor armamentarium and highlights the aryl hydrocarbon receptor as a target for drug development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pele
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Alcatrão
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Receptores de Hidrocarboneto Arílico
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Dermatite Atópica
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Disbiose
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Microbiota
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Anti-Infecciosos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Holanda