Differentiation, Fine Structure, Function and Clinical Significance of Kupffer Cells

Kupffer cells are the largest aggregations of macrophages in tissue of the body. They are dominantly lining the lumen of liver sinusoids and show endocytic activity against blood-borne materials that entering liver. In the fetal and adult duration, Kupffer cell differentiation are controlled by growth factors especially (Macrophage colony-stimulating factor M-CSF). Kupffer cells (KCs) are essential liver macrophages originating primarily from three waves of embryonic hematopoiesis. The phenotypic and functional heterogeneity of KCs is significant, affecting their response to various liver injuries. KCs have an important role in keeping liver homeostasis, including the clearance of pathogens and apoptotic cells, and regulating inflammation. In acute liver injury, such as acetaminophen overdose, KCs undergo dynamic changes, initially decreasing in number and later recovering via self-renewal. Chronic liver injuries, like NASH, see a depletion of KCs alongside a recruitment of bone marrow-derived macrophages (BM-KCs) to maintain the macrophage pool. The function of KCs varies notably between embryonic-derived KCs and those derived from bone marrow, influencing their responses in inflammation and tissue repair. Strong evidence indicates that KCs may contribute to tissue remodeling and fibrosis in chronic liver diseases by mediating inflammation and extracellular matrix deposition.