Kupffer Cell Metabolism and Function

Abstract

Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions.

Keywords: Kupffer cells; Liver; Macrophages; Metabolism.

Figure 1. Implication of Kupffer cells in liver injury

Toxic components, bacterial/viral infections and other injuries target hepatocytes. Necrotic hepatocytes release various molecules that activate Kupffer cells. These latter synthesize and secrete important cytokines, chemokines, TNF-α, and TGF-β, allowing the recruitment of inflammatory responses into the injured liver and the activation of HSCs. The inflammatory responses induce chronic inflammation, which induces hepatocyte proliferation and transformation to generate hepatocellular carcinoma. Activation of HSCs drives the synthesis of collagens and specific proteins facilitating fibrogenesis. Activated KCs differentiate into classical M1 or alternative M2 macrophages, which participate in fibrosis or tumor progression or fibrosis resolution and elimination of tumor cells.