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Uncovering a dual T helper 17/type 2 transcriptomic endotype in psoriasis
Chung-Han Chen1, Meng-Sui Lee2, Wen-Yu Chang3
1Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Journal of the American Academy of Dermatology
|July 2, 2026
Summary
Taiwanese psoriasis shows a dual immune response involving Th17 and Type 2 pathways, with high IL-36 activation. This finding highlights the need for tailored psoriasis treatments in this population.
Area of Science:
- Dermatology and Immunology
- Transcriptomics
- Molecular Biology
Background:
- The IL-23/Th17 axis is central to psoriasis, but ethnic variations in its molecular profile are not well understood.
- Psoriasis pathogenesis involves complex immune dysregulation, necessitating deeper molecular characterization across diverse populations.
Purpose of the Study:
- To define the immunological and pathogenic transcriptomic profiles of a Taiwanese psoriasis cohort.
- To identify molecular differences and potential biomarkers for psoriasis severity in Taiwanese individuals.
Main Methods:
- Bulk RNA-sequencing of lesional skin (LS), non-lesional skin (NL), and normal skin (N) from psoriasis patients and healthy controls.
- Differential gene expression (DEG) analysis, Gene Set Enrichment Analysis (GSEA), and correlation analysis with Psoriasis Area and Severity Index (PASI) scores.
- ELISA validation of serum cytokine levels in a larger cohort of psoriasis patients and controls.
Main Results:
- Identified 4,694 differentially expressed genes (DEGs) in lesional vs. normal skin, confirming Th17 pathway activation (IL-17A/C, IL-23A).
- Revealed a significant dual immune dysregulation with upregulation of Type 2 (Th2) signatures (IL-4R, CCL17, TSLP) and extreme IL-36 family activation (IL-36G).
- Observed downregulation of skin barrier genes (KRT77, GJB4) and identified IL-36RN and AREG/CDSN as potential psoriasis severity biomarkers.
Conclusions:
- Taiwanese psoriasis exhibits a unique dual Th17/Type 2 endotype with pronounced IL-36 pathway activation.
- Transcriptomic findings suggest the need for ethnicity-specific therapeutic strategies for psoriasis.
- Limitations include a small sample size and focus on a single ethnic group, with findings representing associations rather than direct causality.
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