Work

MAIT Cells with High PFN1 Expression Mediate Immune Activation and Metabolic Reprogramming in Psoriasis

Year: 2025

Type: article

Abstract: 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.

Source: Clinical Cosmetic and Investigational Dermatology

DOI: 10.2147/ccid.s535795

Authors: Man-Ning Wu, Yue-Min Zou, Xiang-Nan Zhou, Sangwon Hong, Lei Wang, Yan-Ping Bai

Institutions: Beijing University of Chinese Medicine, China-Japan Friendship Hospital

Language: English

Topic: Psoriasis: Treatment and Pathogenesis

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836