Macrophage Notch1 signaling modulates regulatory T cells via the TGFB axis in early MASLD.

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), were used to investigate the role of Tregs in early MASLD and the effect of hepatic macrophage Notch1 signaling on Treg frequency.

Targeting macrophagic 17-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17-hydroxysteroid dehydrogenase type 7 (17-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization.