Repurposed fludarabine alleviates type 1 diabetes through the dual effects on dendritic cell activation and β cell ferroptosis

Mechanistically, fludarabine directly binds to STAT1 and disrupts its interaction with the aryl hydrocarbon receptor (AHR), thereby facilitating AHR nuclear translocation. Activated AHR transcriptionally upregulates anti-inflammatory and anti-ferroptotic programs, conferring a tolerogenic DC phenotype and protecting β cells from stress-induced ferroptosis. Collectively, our findings identify fludarabine as a promising immunometabolic therapeutic candidate that restores immune tolerance and enhances β cell resilience, which could be a viable approach against T1D in clinical settings.