Uncovering a dual T helper 17/type 2 transcriptomic endotype in psoriasis

The interleukin (IL) 23/T helper (Th) 17 axis is the cornerstone of psoriasis pathogenesis, but molecular heterogeneity across different ethnicities remains poorly defined.

To comprehensively define the immunological and pathogenic transcriptomic profiles of a Taiwanese cohort with psoriasis.

Lesional skin and nonlesional skin biopsies from 11 patients with chronic plaque psoriasis and normal-appearing skin from 9 healthy controls were analyzed via bulk RNA sequencing. Differential gene expression, pathway enrichment (Gene Set Enrichment Analysis), and clinical correlations (Psoriasis Area and Severity Index score) were performed. Serum levels of cytokines were validated via enzyme-linked immunosorbent assay from all 50 patients with psoriasis and 9 healthy controls.

Analysis identified 4694 differential gene expressions in lesional skin versus normal-appearing skin. We confirmed robust Th17 upregulation (IL-17A/C and IL-23A). Unanticipatedly, a profound dual immune dysregulation was identified, involving significant upregulation of type 2 (Th2) signatures (IL-4R, CCL17, and TSLP). The IL-36 family was the most highly activated cytokine axis (IL-36Glog₂ fold change = 5.5). Barrier function genes (KRT77 and GJB4) were significantly downregulated. Correlation analysis identified IL-36RN and the combination of amphiregulin (AREG)/corneodesmosin (CDSN) (r ≈ -0.9, P = .002) as potential severity biomarkers.

The limitations included small sample size and focus on a single ethnic group. Transcriptomic findings represent associations rather than mechanistic evidence of pathogenesis.

Psoriasis in Taiwanese patients 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.