Man-Ning Wu,1– 3 Yue-Min Zou,1– 3 Xiang-Nan Zhou,2,3 Sangwon Hong,1– 3 Lei Wang,2,3 Yan-Ping Bai2,3 

1Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Dermatology, China-Japan Friendship Hospital, National Center for Integrative Medicine, Beijing, People’s Republic of China; 3Department of Dermatology, China-Japan Friendship Hospital, Beijing, People’s Republic of China

Correspondence: Yan-Ping Bai, Email zhi@tsinghua.edu.cn Lei Wang, Email wanglei010zyy@163.com

Background: Psoriasis is a chronic inflammatory skin disease involving dysregulated immune responses and complex genetic factors. This study combines single-cell RNA sequencing (scRNA-seq), gene expression profiling, and genetic analysis to explore cellular and molecular contributors to psoriasis.
Methods: Single-cell RNA-seq data (n = 3 psoriasis, n = 2 control; GSE228421) were used for cell-type annotation and functional characterization. T cell subsets were analyzed for differentiation trajectories and cell-cell communication. Differentially expressed genes in mucosal-associated invariant T (MAIT) cells were evaluated by enrichment analysis. Candidate gene causality was tested via eQTL-based Mendelian randomization (MR) and supported by bulk RNA-seq validation.
Results: MAIT cells were enriched in psoriatic lesions and exhibited strong intercellular interactions. Functional analyses revealed activation of IL6-JAK-STAT3 signaling, TNF-NFκB pathway, and glycolysis in MAIT cells. MR identified RPS20 as a protective factor (OR = 0.5994, p = 0.011) and PFN1 as a potential risk gene (OR = 1.7229, p = 0.037), with PFN1 highly expressed in MAIT cells. Colocalization analysis showed no significant genetic overlap between PFN1 expression and psoriasis risk. Metabolic profiling revealed differential pathway involvement in PFN1+ and PFN1− MAIT cells.
Conclusion: Our integrative analysis highlights MAIT cells and PFN1 as likely contributors to psoriasis pathogenesis. These findings offer insights into immune and metabolic alterations, suggesting potential targets for therapeutic intervention.

Keywords: psoriasis, MAIT cells, PFN1, scRNA-seq, eQTL Mendelian randomization analysis