From model to man: Understanding Tregs' dual role in MASLD

Background instead, this increase correlated with greater disease severity. With progressing metabolic inflammation, an increased proportion of Tregs also expressed IL-17, which correlated with more severe liver pathology. Conclusions: 17-skewed) cells. These findings highlight the complex role of adaptive immunity in MASH progression and provide potential targets for future immunomodulatory therapies. Impact and implications: T cells markedly amplify hepatocellular injury and fibrosis. By separating initiating (macrophage-driven) from amplifying (adaptive) immune signals, our study refines current pathogenic models and provides hepatologists and immunologists with stage-specific therapeutic targets. For clinicians and trial designers, the data indicate that stabilizing Tregs or selectively dampening pro-inflammatory T-cell subsets could complement metabolic interventions in metabolic dysfunction-associated steatotic liver disease/steatohepatitis, whereas indiscriminate Treg expansion might be counter-productive. Because the conclusions are drawn from a murine model, translation to humans will require validation in patient-derived tissues and non-invasive immune biomarkers.