Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH
Sabine Daemen, Anastasiia Gainullina, Gowri Kalugotla, Li He, Mandy M. Chan, Joseph W. Beals, Kim Liss, Samuel Klein, Ariel E. Feldstein, Brian N. Finck, Maxim N. Artyomov, Joel D. Schilling
Abstract
macrophages accumulate. In concert, monocyte-derived infiltrating macrophages enter the liver and consist of a transitional subset that expresses Cx3cr1/Ccr2 and a second subset characterized by expression of Trem2, Cd63, Cd9, and Gpmnb; markers ascribed to lipid-associated macrophages (LAMs). The Cx3cr1/Ccr2-expressing macrophages, referred to as C-LAMs, localize to macrophage aggregates and hepatic crown-like structures (hCLSs) in the steatotic liver. In C-motif chemokine receptor 2 (Ccr2)-deficient mice, C-LAMs fail to appear in the liver, and this prevents hCLS formation, reduces LAM numbers, and increases liver fibrosis. Taken together, our data reveal dynamic changes in liver macrophage subsets during the pathogenesis of NASH and link these shifts to pathologic tissue remodeling.