Integrating Bioinformatics and Experimental Validation Identifies SCD as a Ferroptosis-Related Immune Regulator and Therapeutic Target in Crohn's Disease.

Abstract

This study investigates the role of ferroptosis-related genes (FRGs) in the intestinal inflammation of Crohn's disease (CD). Through integrated bioinformatics and experimental validation, we identified differentially expressed genes from RNA-seq data and intersected them with known FRGs to obtain ferroptosis-related differentially expressed genes (FEDGs). Functional enrichment and immune infiltration analyses were performed, and seven hub FEDGs were selected using machine learning. A diagnostic model based on these genes showed strong predictive ability. Immune analysis revealed significant associations with macrophages, neutrophils, dendritic cells, and CD4+ T cells. Protein expression of key hub genes was validated in clinical CD samples and a DSS-induced colitis model. Importantly, localized inhibition of SCD alleviated disease severity in experimental colitis. These findings highlight the involvement of ferroptosis in CD immune dysregulation and propose SCD as a potential therapeutic target.