Monocytes and Macrophages as Unique Cellular Compartments Governing Non-Alcoholic Fatty Liver Disease and Inflammation.

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is a spectrum of liver diseases from simple steatosis to the most severe form of hepatocellular carcinoma. Liver injuries resulting from various factors, including viral infections, alcohol consumption, and metabolic disorders, trigger the activation of resident immune cells and the recruitment of circulating immune cells to the liver. This chronic inflammatory environment leads to tissue damage and the progression of liver fibrosis. Macrophages are highly versatile immune cells that play a dual role in fibrosis: they contribute to the progression of fibrosis (M1 and Ly6c^high macrophages) and its resolution (M2 and Ly6c^low macrophages). M1 macrophages and those with high surface expression of Ly6C exhibit pro-inflammatory characteristics, while M2 macrophages and myeloid cells with low expression of Ly6C mitigate inflammation and inhibit fibrosis progression. Environmental stimuli influence the complex mechanisms hepatic macrophages regulate the fibrosis they encounter. Kupffer cells initiate the inflammatory cascade and recruit monocyte-derived macrophages, which modulate the propagation of fibrosis and promote fibrinolysis. Additionally, hepatic macrophages interact with other cell types through exosomes, facilitating the transfer of cellular components that influence the outcome of liver fibrosis. In this review, the critical role of macrophages in inflammation-induced fibrosis and tissue restoration is discussed.