Macrophages in cholangiopathies

Cholangiopathies are a heterogeneous class of liver diseases where cholangiocytes are the main targets of liver injury. Although available and emerging therapies mainly target bile acids (ursodeoxycholic acid/UDCA, 24-Norursodeoxycholic acid/norUDCA) and related signaling pathways (obeticholic acid, fibrates, FXR, and PPAR agonists), the mechanisms underlying inflammation, ductular reaction and fibrosis in cholestatic liver diseases remain poorly understood.Data from patients with cholestatic diseases, such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) as well as mouse models of biliary injury emphasize the role of immune cells in the pathogenesis of cholestatic disorders and indicate diverse functions of hepatic macrophages. Their versatile polarization phenotypes and their capacity to interact with other cell types (e.g. cholangiocytes, other immune cells) make macrophages central actors in the progression of cholangiopathies.In this review, we summarize recent findings on the response of hepatic macrophages to cholestasis and biliary injury and their involvement in the progression of cholangiopathies. Furthermore, we discuss how recent discoveries may foster the development of innovative therapies to treat patients suffering from cholestatic liver diseases, in particular, treatments targeting macrophages to limit hepatic inflammation.