A shared tissue transcriptome signature and pathways in psoriasis and ulcerative colitis

Area of Science:

• Immunology
• Genetics
• Dermatology and Gastroenterology

Background:

• Psoriasis (PS) and Ulcerative Colitis (UC) share therapies, yet their common pathophysiology is poorly understood.
• Identifying shared molecular mechanisms is crucial for understanding and treating these distinct inflammatory diseases.

Approach:

• A meta-analysis of transcriptomic data from lesional and nonlesional tissues in UC and PS patients was performed.
• Differentially expressed genes (DEGs) were identified, and a shared gene signature between the two diseases was defined.
• Pathway enrichment analysis was conducted to identify commonly dysregulated molecular pathways.

Key Points:

• A shared gene signature of 190 DEGs common to both PS and UC was identified.
• Commonly dysregulated pathways include interferon signaling (IFI6, CXCL9-11), IL-23 pathway (IL-23A, CCL20, PI3, CXCL1, LCN2), and Th17 pathway.
• Elevated ICOS and CTLA4 suggest T-cell activation in both conditions.

Conclusions:

• This is the first transcriptomic meta-analysis to define a shared tissue gene signature and dysregulated pathways in PS and UC.
• The findings suggest that similar immune mechanisms initiate and sustain inflammation in both psoriasis and ulcerative colitis.
• A gene set improvement score demonstrated the clinical value of the shared signature in reflecting treatment response.