Multi-omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis

Area of Science:

• Dermatology
• Microbiology
• Genomics

Background:

• The precise pathogenesis of psoriasis remains incompletely explored.
• Understanding the interplay between host genetics and the skin microbiome is crucial for developing targeted therapies.

Purpose of the Study:

• To elucidate the underlying mechanisms of psoriasis using a systems biology approach.
• To investigate the associations between host defense gene expression and skin microbiota composition in psoriasis patients.

Main Methods:

• Collected skin biopsies and swabs from lesional and non-lesional skin of psoriasis patients, psoriatic arthritis patients, and healthy controls.
• Performed high-throughput RNA-sequencing for gene expression profiling and 16S rRNA sequencing for metagenomic analysis.
• Analyzed associations between transcriptome and microbiome data using co-expression gene networks.

Main Results:

• Lesional and non-lesional skin samples showed distinct transcriptome profiles, with significant enrichment in neutrophil activation pathways.
• A core gene module associated with local psoriasis severity was identified, involving neutrophil activation, epidermal differentiation, and bacterial response.
• Specific bacterial taxa (Enhydrobacter, Micrococcus, Leptotrichia) were significantly correlated with the core gene network.

Conclusions:

• A core gene network associated with local disease severity and microbiome composition was identified in psoriatic skin.
• This network is implicated in the inflammatory processes and hyperkeratinization characteristic of psoriasis.
• The findings highlight the intricate relationship between host genetics and the skin microbiome in psoriasis pathogenesis.