A human single-cell atlas identifies OLR1(+) scar-associated macrophages as a potential therapeutic target for chronic liver disease.

OLR1(+) scar-associated macrophages are spatially enriched in fibrotic liver tissue and linked to increased fibrosis in chronic liver disease.

• Why it matters: Understanding which macrophage subpopulations drive fibrosis can reveal targeted therapies for CLD, but the specific cells involved remain unclear.
• What they did: A liver single-cell atlas of 649,295 cells from healthy and CLD patients identified two disease-expanded TREM2+ macrophage types, including OLR1+ pro-inflammatory SAMac, with spatial and expression analyses.
• The result: High hepatic OLR1 expression correlates with increased fibrosis and worse outcomes, and targeting macrophage OLR1 reduces fibrogenic activity in models, suggesting OLR1 as a therapeutic target.