Innate Immune Cells in Immune Tolerance After Liver Transplantation

Abstract

Currently, liver transplantation is the most effective treatment for end-stage liver disease. Immunosuppressive agents are required to be taken after the operations, which have significantly reduced rejection rates and improved the short-term (<1 year) survival rates. However, post-transplant complications related to the immunosuppressive therapy have led to the development of new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. Donor specific immune tolerance, which means the mature immune systems of recipients will not attack the grafts under the conditions without any immunosuppression therapies, is considered the optimal state after liver transplantation. There have been studies that have shown that some patients can reach this immune tolerance state after liver transplantation. The intrahepatic immune system is quite different from that in other solid organs, especially the innate immune system. It contains a variety of liver specific cells, such as liver-derived dendritic cells, Kupffer cells, liver sinusoidal endothelial cells, liver-derived natural killer (NK) cells, natural killer T (NKT) cells, and so on. Depending on their specific structures and functions, these intrahepatic innate immune cells play important roles in the development of intrahepatic immune tolerance. In this article, in order to have a deeper understanding of the tolerogenic functions of liver, we summarized the molecular mechanisms of immune tolerance induced by intrahepatic innate immune cells after liver transplantation.

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

“…Hepatic ischemia, drug-induced liver injury, and viral and autoimmune hepatitis are among pathogens and by maintaining tolerance to foodborne and bacterial antigens from the intestine [22,23]. Although KCs are able to process and present antigens [24], they express MHC -II and costimulatory molecules in significantly lower levels than dendritic cells [25]. Furthermore, they secrete high levels of the T-cell inhibitory molecule PDL-1 and IL-10, which induces expansion and activation of regulatory T cells [26].…”

Liver Macrophages: Old Dogmas and New Insights

“…variety of activating signals. As a consequence, numerous reviews are available on the crucial roles of hepatic macrophages in liver cancer, (7)(8)(9) fibrosis, (6,10,11) alcoholic liver disease and bacterial infections, (12)(13)(14)(15)(16) nonalcoholic fatty liver disease, (17)(18)(19) viral hepatitis, (20) cholestatic diseases, (21,22) drug-induced acute liver injury, (23,24) ischemia reperfusion injury and liver transplant, (25,26) liver regeneration, (23,27,28) and also in aging liver. (29) Because our knowledge on macrophages in the context of liver disease has increased exponentially over recent years, a fresh view on this fascinating immune cell population has emerged, challenging some old dogmas and highlighting the heterogeneity and plasticity of liver macrophages.…”

Role of Innate Immunity in Pediatric Post-transplant Idiopathic Liver Fibrosis

“…There are a large number of innate immune cells involved in immune recognition and response, including Kupffer cells, dendritic cells, natural killer cells, NKT cells, neutrophils, and so on. These innate immune cells are involved in constituting the hepatic immune microenvironment and activate adaptive immune responses (17). Other components also play roles in this process, such as pattern recognition receptors [e.g., Tolllike receptors (TLR) and humoral factors] (e.g., complement and IFN).…”