The immunophenotype of antigen presenting cells of the mononuclear phagocyte system in normal human liver – A systematic review

Abstract

The mononuclear phagocytic system (MPS), comprised of monocytes, macrophages, and dendritic cells, is essential in tissue homeostasis and in determining the balance of the immune response through its role in antigen presentation. It has been identified as a therapeutic target in infectious disease, cancer, autoimmune disease and transplant rejection. Here, we review the current understanding of the immunophenotype and function of the MPS in normal human liver. Using well-defined selection criteria, a search of MEDLINE and EMBASE databases identified 76 appropriate studies. The majority (n=67) described Kupffer cells (KCs), although the definition of KC differs between sources, and little data were available regarding their function. Only 10 papers looked at liver dendritic cells (DCs), and largely confirmed the presence of the major dendritic cell subsets identified in human blood. Monocytes were thoroughly characterized in four studies that utilized flow cytometry and fluorescent microscopy and highlighted their prominent role in liver homeostasis and displayed subtle differences from circulating monocytes. There was some limited evidence that liver DCs are tolerogenic but neither liver dendritic cell subsets nor macrophages have been thoroughly characterized, using either multi-colour flow cytometry or multi-parameter fluorescence microscopy. The lobular distribution of different subsets of liver MPS cells was also poorly described, and the ability to distinguish between passenger leukocytes and tissue resident cells remains limited. It was apparent that further research, using modern immunological techniques, is now required to accurately characterize the cells of the MPS in human liver.

Amphiphilic core shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells

“…The effective transfection is probably attributed to the special function of KCs, which could identify and engulf the miRNA-loaded PEI@PMMA NPs as foreign or harmful materials. 28 Similar results have been reported by using other types of NPs. 29,30 However, the detailed targeting mechanism of PEI@PMMA NPs still needs to be investigated in our further work.…”

Monocyte and Macrophage Plasticity in Tissue Repair and Regeneration

“…2 These cells differentiate and enter the systemic circulation to form monocytes, and then infiltrate into tissues to become macrophages. 3 The other cells of the MPS (ie, DCs and macrophages) also have a remarkable heterogeneity related to their origin, phenotype, tissue localization, proliferative potential, and functions.…”

Immunofluorescence identifies distinct subsets of endothelial cells in the human liver

“…Other non-parenchymal cells in the liver such as KCs have yet to be thoroughly characterized, but are also clearly heterogeneous 42 . Whether or not this heterogeneity follows an acinar distribution will provide insights into the roles these cells play in health and disease.…”