Myeloid-derived Suppressor Cells in Metabolic Dysfunction-associated Fatty Liver Disease

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a rapidly increasing global health concern, driven by metabolic stress, chronic inflammation, and progressive fibrotic remodeling. Myeloid-derived suppressor cells (MDSCs) have emerged as pivotal yet context-dependent modulators of MAFLD pathogenesis. This review summarizes the biological characteristics of MDSCs, their immunosuppressive mechanisms, and their multifaceted roles in MAFLD progression, including hepatic steatosis, chronic inflammation, and fibrogenesis. Quantitative synthesis reveals that murine models demonstrate MDSC expansion (∼3-fold with a high-fat diet, P < 0.05) and suppression of MDSC-associated proinflammatory mediators (e.g., MitoTEMPO reduced hepatic S100A8 mRNA by 5.9-fold, P < 0.001). In one human cohort (n = 98), hepatic CD33+/HLA-DR− MDSC density correlated with inflammation grade (Spearman r = 0.610, P < 0.001) and fibrosis stage (r = 0.687, P < 0.001), though this cross-sectional dataset lacked MAFLD-specific stratification and longitudinal validation. We further discuss emerging MDSC-targeted strategies and explicitly acknowledge current translational gaps. Collectively, this review provides a mechanistic and critically appraised framework positioning MDSCs as both promising therapeutic targets and potential biomarkers for MAFLD.