The role of macrophage TAM receptor family in the acute-to-chronic progression of liver disease: From friend to foe?

Hepatic macrophages, the key cellular components of the liver, emerge as essential players in liver inflammation, tissue repair and subsequent fibrosis, as well as tumorigenesis. Recently, the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl and MerTK, was found to be a pivotal modulator of macrophages. Activation of macrophage TAM receptor signalling promotes the efferocytosis of apoptotic cells and skews the polarization of macrophages. After briefly reviewing the mechanisms of TAM receptor signalling in macrophage polarization, we focus on their role in liver diseases from acute injury to chronic inflammation, fibrosis and then to tumorigenesis. Notably, macrophage TAM receptor signalling seems to be a two-edged sword for liver diseases. On one hand, the activation of TAM receptor signalling inhibits inflammation and facilitates tissue repair during acute liver injury. On the other hand, continuous activation of the signalling contributes to the process of chronic inflammation into fibrosis and tumorigenesis by evoking hepatic stellate cells and inhibiting anti-tumour immunity. Therefore, targeting macrophage TAM receptors and clarifying its downstream pathways will be exciting prospects for the precaution and treatment of liver diseases, particularly at different stages or statuses.