Effector Mechanisms Of Innate Immune Cells In Liver Injury And Regeneration

The liver is one of largest digestive organs in the body and carries on the functions in secretion of bile, synthesis of vital proteins and detoxification. Distinct with other organs, liver has a special double blood supply, liver artery and portal vein. In view of such special anatomical location and function, the liver is continuously exposed in the large load of the intestinal antigen that includes pathogens, toxins, tumor cells and harmless dietary antigens, making the liver not only bear "internal depurating blood" function, but also remove the foreign matter of intestinal source. It is speculated that these characteristics provide with the possibility that liver is endowed with a unique fast alternative immune response mechanism in response to the liver-specific potential danger signals. It is now being appreciated that innate immune response serves as the first line of defense against invading pathogens and the local immune mechanisms are required to cope with these diverse immunological challenges. It has been known that the liver is a site for the production of cytokines, complement components and acute phase proteins and contains large numbers of phagocytes, antigen-presenting cells and lymphocytes. According to the high proportion of innate immune cells and rapid responses to the stimuli in the liver, it is supposed that liver is a lymphoid organ with innate immune features, responding rapidly and functioning nonspecifically and with no memory. Therefore, a new subspecialty through combination of hepatology with immunology termed "hepatoimmunology" has emerged. Many studies have revealed that these innate immune cells abundant in the liver play a critical role in the immunosurveillance, such as protection from infection with bacteria, parasite, and virus. Meanwhile, some unexpected auto-attacks against hepatocytes mediated by over-activated innate immune cells in the live have often been found on some occasions. Our theme is to explore the roles of hepatic innate immune cells in the immune-mediated liver injury and repair, and mainly try to give answers to the following scientific questions: to establish a novel NK cell-mediated murine hepatitis model to facilitate the investigation of the NK cell role in autoimmune liver diseases; to further explore the dispensable role of NK cell in Concanavalin A-induced hepatitis; and to investigate the negative regulation of liver regeneration by hepatic innate...