TREM2-expressing macrophages in liver diseases

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the global population and spans a spectrum of liver abnormalities, including simple steatosis, inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent studies have identified triggering receptors expressed on myeloid cells 2 (TREM2)-expressing macrophages as key regulators of MASLD progression. TREM2 plays a pivotal role in regulating macrophage-mediated processes such as efferocytosis, inflammatory control, and fibrosis resolution. Additionally, soluble TREM2 (sTREM2) was proposed as a noninvasive biomarker for diagnosing and monitoring MASLD progression. However, the molecular mechanisms through which TREM2 influences MASLD pathogenesis remain incompletely understood. This review summarizes the current understanding of TREM2-expressing macrophages in MASLD, with the goal of illuminating future research and guiding the development of innovative therapeutic strategies targeting TREM2 signaling pathways.