Single-cell atlas of 77 livers points to OLR1 macrophages in fibrosis
Scar-associated macrophages expressing the scavenger receptor OLR1 accumulate in fibrotic liver tissue. Published in Nature Genetics, the study analyzed 649,295 cells from 42 healthy people and 35 patients with chronic liver disease, resolving 125 distinct cellular states. Between two disease-expanded TREM2 + macrophage types, high hepatic OLR1 expression was associated with increased fibrosis across multiple causes and adverse patient outcomes in metabolic dysfunction-associated steatotic liver disease. Similar cells expanded in mouse chronic liver disease. Targeting macrophage OLR1 attenuated fibrogenic activity in human coculture and multilineage spheroid models.
The findings could guide drug development for liver fibrosis, though evidence for targeting OLR1 so far comes from cell models and mice rather than treated patients.
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