Atopic dermatitis displays stable and dynamic skin transcriptome signatures.

Area of Science:

• Dermatology
• Genomics
• Immunology

Background:

• Atopic dermatitis (AD) skin transcriptome studies reveal broad molecular dysregulation.
• Previous observations relied on microarray data and focused on therapeutic improvements.

Purpose of the Study:

• To investigate the skin transcriptome in AD patients.
• To analyze the impact of systemic treatments (dupilumab, cyclosporine) on AD skin gene expression.

Main Methods:

• mRNA sequencing of skin biopsies from 59 moderate-to-severe AD patients (pre- and post-treatment) and 31 healthy controls.
• Analysis included differential gene expression, pathway enrichment, correlation, and coexpression networks.

Main Results:

• A stable 'core' signature in AD skin involves disrupted epidermal differentiation and IL-31/IL-1 signaling.
• A dynamic signature shows type 2 inflammation, TH17 signaling, and NK cell activity.
• Cyclosporine promoted greater transcriptome reversion; dupilumab enhanced epidermal differentiation markers. Both reduced type 2 markers, but skin profiles remained altered compared to healthy controls.
• Specific gene expression patterns (low IL4RA/IL13, high IL36A) correlated with dupilumab response.

Conclusions:

• The AD core signature involves keratinocyte differentiation and itch signaling gene dysregulation.
• Dynamic signatures reflect progressive immune responses involving type 2, TH17, and NK cell signaling.
• While treatments improve AD skin transcriptome, significant differences from healthy skin persist.