The IL-23/Th17 axis is the cornerstone of psoriasis pathogenesis, but molecular heterogeneity across different ethnicities remains poorly defined.
Objective
To comprehensively define the immunological and pathogenic transcriptomic profiles of a Taiwanese psoriasis cohort.
Methods
Lesional skin (LS) and non-lesional skin (NL) biopsies from 11 patients with chronic plaque psoriasis and normal skin (N) from 9 healthy controls were analyzed via bulk RNA-sequencing. Differential gene expression (DEG), pathway enrichment (GSEA), and clinical correlations (PASI score) were performed. Serum levels of cytokines were validated via ELISA from all 50 psoriasis patients and 9 healthy controls.
Results
Analysis identified 4,694 DEGs in LS vs. N. We confirmed robust Th17 upregulation (IL-17A/C, IL-23A). Unanticipatedly, a profound dual immune dysregulation was identified, involving significant upregulation of Type 2 (Th2) signatures (IL-4R, CCL17, TSLP). The IL-36 family was the most highly activated cytokine axis (IL-36G log2FCH=5.5). Barrier function genes (KRT77, GJB4) were significantly downregulated. Correlation analysis identified IL-36RN and the combination of AREG/CDSN (r ≈ -0.9, p=0.002) as potential severity biomarkers.
Limitations
The small sample size and focus on a single ethnic group. Transcriptomic findings represent associations rather than mechanistic evidence of pathogenesis.
Conclusion
Taiwanese psoriasis is characterized by a dual Th17/Type 2 endotype and extreme IL-36 activation. This molecular landscape underscores the need for stratified therapeutic strategies in Taiwanese populations.
