The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced inflammatory subtype, metabolic dysfunction-associated steatohepatitis (MASH), are becoming increasingly prevalent liver disorders driven by complex interactions between metabolic stress, immune dysregulation, and fibrotic remodeling. Regulatory T cells (Tregs), traditionally recognized for their immunosuppressive functions, have emerged as key modulators of hepatic inflammation, fibrosis, and systemic metabolic balance. While Tregs can suppress pro-inflammatory immune responses and mitigate liver injury, accumulating evidence highlights their paradoxical roles in liver fibrosis, including the promotion of hepatic stellate cell activation and profibrotic remodeling. This review critically examines the dual and context-dependent roles of Tregs in MASLD and MASH, emphasizing implications for therapeutic intervention. Additionally, we discuss current preclinical strategies aimed at modulating Treg abundance and function, highlighting the challenges and opportunities associated with developing stage-specific therapeutic approaches that consider not only local hepatic effects but also potential systemic metabolic consequences.