2023, Vol. 27 ›› Issue (24): 3901-3909

Mechanism of Kupffer cells in immune tolerance after liver transplantation

Wang Yaoquan, Xuan Juanjuan, Zhang Jixiang, Chen Kaige, Chen Guoyong, Wei Sidong   

Abstract: BACKGROUND: Immune rejection after liver transplantation seriously affects the quality of life of patients. The establishment of long-term immune tolerance still faces many problems. Kupffer cells play an important role in inhibiting liver transplantation rejection and promoting immune tolerance.
OBJECTIVE: To review the role of Kupffer cells in immune tolerance after liver transplantation and its mechanism, in order to provide reference ideas for establishing immune tolerance in liver transplantation.
METHODS: In December 2021, the first author used computers to search the relevant literature from January 1970 to December 2021 in PubMed and CNKI databases using “Kupffer cells, liver transplantation” as the English and Chinese search terms, respectively. Finally, 73 articles were included for further analysis.
RESULTS AND CONCLUSION: (1) Kupffer cells are macrophages resident in the liver. There are many specific receptors and binding sites on the surface of Kupffer cells, including complement receptors, Toll-like receptors, and other pathogen recognition receptors, which can quickly respond to the changes of tissue environment and present different cell phenotypes, that is, M1 and M2 Kupffer cells. Liver transplantation immune tolerance is closely related to M2 Kupffer cells. (2) Kupffer cells exert vital roles in the establishment of immune tolerance after transplantation through the mechanisms of cell phagocytosis, cell polarization, antigen presentation, cell membrane proteins, and cytokines. However, there is still a lack of high-quality basic and clinical research. (3) Existing research on Kupffer cells indicates that a variety of cytokines and non-specific factors may be associated with immune tolerance after transplantation, mainly including T cell immunoglobulin domain and mucin domain 4, F1 type scavenger receptor, antigenic calreticulin, protein disulfide isomerase, inhibitory histone deacetylase 11, heat shock protein, X-box binding protein 1, bone marrow mesenchymal stem cells, interleukin 2, interleukin 4, interleukin 6, interleukin 10, interleukin 17, interleukin 23, interleukin 34, complement, Fas-FasL, Toll-like receptors, prostaglandins, transforming growth factor β and interferon γ. (4) In terms of basic research, constructing an orthotopic liver transplantation animal model helps further explore the effect of different functions of Kupffer cells on the establishment of immune tolerance after liver transplantation. (5) In terms of clinical application, we can predict and promote the establishment of immune tolerance through the pathological analysis of the graft, Kupffer cytokine expression in transplants, gene detection, and donor infusion of bone marrow mesenchymal stem cells. However, multi-center, large-sample clinical studies are warranted in the future.

Key words: Kupffer cell, macrophage, liver transplantation, rejection, immune tolerance, mechanism, liver disease, organ transplantation