库普弗细胞在肝移植免疫耐受中的机制  

Mechanism of Kupffer cells in immune tolerance after liver transplantation

作　　者：王耀权 轩娟娟 张继翔 陈凯歌 陈国勇 魏思东 Wang Yaoquan;Xuan Juanjuan;Zhang Jixiang;Chen Kaige;Chen Guoyong;Wei Sidong(People’s Hospital of Henan University,Zhengzhou 450003,Henan Province,China)

机构地区：[1]河南大学人民医院,河南省郑州市450003

出　　处：《中国组织工程研究》2023年第24期3901-3909,共9页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(U2004124),项目负责人:陈国勇;河南省医学科技攻关计划项目(SBGJ2018071),项目负责人:陈国勇;河南省医学科技攻关计划项目(SB201903020),项目负责人:魏思东;河南省科技攻关计划项目(212102310717),项目负责人:魏思东。

摘　　要：背景:肝移植后的免疫排斥反应严重影响患者的生存质量,长期免疫耐受的建立仍然面临着许多问题,而库普弗细胞在抑制肝移植排斥反应及促进免疫耐受方面发挥着重要作用。目的:综述库普弗细胞在肝移植免疫耐受中的作用及其机制的研究进展,旨在为建立肝移植免疫耐受提供参考思路。方法:第一作者于2021年12月应用计算机在PubMed和中国知网数据库检索1970年1月至2021年12月相关文献,以“Kupffer cells,liver transplantation”为英文检索词,以“库普弗细胞、肝移植”为中文检索词,最终纳入73篇文献进行分析。结果与结论:(1)库普弗细胞是驻留在肝脏内的巨噬细胞,其表面存在包括补体受体、Toll样受体和其他病原体识别受体在内的多种特异性受体和结合位点,能够快速响应组织环境的变化,根据需要呈现不同的细胞表型,即M1型和M2型库普弗细胞,而肝移植免疫耐受与M2型库普弗细胞关系密切。(2)库普弗细胞通过细胞吞噬、细胞极化、抗原呈递、细胞膜蛋白和细胞因子的作用等机制在移植后免疫耐受的建立中发挥重要作用,但是目前尚缺乏高质量的基础和临床研究。(3)目前已有的库普弗细胞的研究中,研究者们已发现多种库普弗细胞中的细胞因子和非特异性因子可能与移植后免疫耐受关联,主要包括T细胞免疫球蛋白结构域和黏蛋白结构域4、F1型清道夫受体、抗原钙网蛋白、蛋白二硫键异构酶、抑制组蛋白脱乙酰酶11、热休克蛋白、X-box结合蛋白1、骨髓间充质干细胞、白细胞介素2、白细胞介素4、白细胞介素6、白细胞介素10、白细胞介素17、白细胞介素23、白细胞介素34、补体、凋亡因子Fas-FasL、Toll样受体、前列腺素、转化生长因子β和干扰素γ。(4)在基础研究方面,通过构建原位肝移植动物模型有助于深入探究库普弗细胞不同功能对肝移植后免疫耐受建立的影BACKGROUND:Immune rejection after liver transplantation seriously affects the quality of life of patients.The establishment of long-term immune tole rance still faces many pro blems.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 mechanis m,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 recepto rs and binding sites on the surfa ce of Kupffer cells,including complement recepto rs,Toll-like receptors,and other pathogen recognition recepto rs,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 M2Kupffer cells.(2)Kupffer cells exert vital roles in the establishment of immune tolerance after transplantation thro ugh 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 Ku pffer cells indicates that a va riety of cyto kines 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 recepto r,antigenic calreticulin,protein disulfide isomerase,inhibitory histone deacetylase 11,heat shock protein,X-box binding protein 1,bone marrow mesenchymal stem cells,inte rleukin 2,interleukin 4,interleukin 6,interleukin 1

关 键 词：库普弗细胞 巨噬细胞 肝移植 排斥反应 免疫耐受 机制研究 肝脏疾病 器官移植 

分 类 号：R458[医药卫生—治疗学] R363[医药卫生—临床医学] R364