CD163

Cell biology

Linguistics

Philosophy

Biology

Chemokine

Steatohepatitis

CD68

Fibrosis

Biochemistry

Tissue remodeling

Fatty liver

Immunology

CCR2

In vitro

Macrophage

Inflammation

Chemokine receptor

Medicine

Chemistry

Composition (language)

CCL2

Immunohistochemistry

Disease

Pathogenesis

CX3CR1

Pathology

Cell Reports

Macrophage-mediated inflammation is critical in the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we describe that, with high-fat, high-sucrose-diet feeding, mature TIM4pos Kupffer cells (KCs) decrease in number, while monocyte-derived Tim4neg 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.

Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH