ArticleJHEP reports : innovation in hepatology2025
Macrophage Notch1 signaling modulates regulatory T cells via the TGFB axis in early MASLD.
Article in JHEP reports : innovation in hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease.Pharmaceutics · 2026Review
- Immunopathogenic mechanisms and immunoregulatory therapies in MASLD.Cellular & molecular immunology · 2025Review
- Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Macrophage-tregs crosstalk: the "hub" of the immune network in MASLD.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background & Aims: Hepatic immune imbalance is crucial for driving metabolic dysfunction-associated steatotic liver disease (MASLD) progression. However, the role of hepatic regulatory T cells (Tregs) in MASLD initiation and the mechanisms responsible for their change are not completely understood. Methods: A mouse model subjected to a short-term high-fat diet (HFD) to mimic early steatosis, along with liver biopsy samples from patients with simple steatosis, and macrophage-specific Notch1-knockout mice (Notch1 Results: A decrease in Tregs contributed to HFD-induced hepatic steatosis and insulin resistance (five/group/time point, Conclusions: These findings highlight the crucial role of hepatic Tregs during the early stage of MASLD and add a novel, non-negligible pathway for macrophage involvement in hepatic steatosis. We identify a previously unrecognized molecular mechanism involving the macrophage Notch1/exosomal miR-142a-3p/TGFBR1 pathway in regulating Treg differentiation, providing a rationale for refined therapeutic strategies for MASLD. Impact and implications: The immune mechanisms driving MASLD progression, particularly during the early stages of disease, are not fully understood, which limits the development of effective interventions. This study elucidated a novel mechanism by which hepatic macrophage Notch1 signaling modulated Tregs through the exosomal miR-142a-3p/TGFBR1 axis, contributing to the progression of MASLD. These findings provide a rationale for a potential immunological approach to treat MASLD in the future.
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