ATG5 overexpression enhances the therapeutic efficacy of mesenchymal stem cells in a mouse colitis model by augmenting anti-inflammatory and antioxidative mechanisms

• ATG5 overexpression in MSCs enhances autophagy and antioxidant capacity, improving their survival and therapeutic potential in inflammatory microenvironments. • MSCs-ATG5 promotes M2 macrophage polarization and suppresses IL-17/NF-κB signaling, reducing colitis severity in a mouse model. • Multiomics analysis reveals that ATG5-engineered MSCs modulate oxidative stress and anti-inflammatory metabolites like PGD2, offering a comprehensive mechanism. • This study provides a novel strategy to enhance MSC-based therapy for IBD by genetic engineering, addressing key limitations in clinical translation.