单位：[1]Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing 101100, China临床科室国家中心普外分中心普外四科（肝脏移植外科）首都医科大学附属北京友谊医院[2]Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing 101100, China[3]National Clinical Research Center for Digestive Diseases, Beijing 101100, China d Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 101100, China临床科室国家中心肝病分中心首都医科大学附属北京友谊医院
Background: Graft-infiltrated dendritic cells (DCs) and CD8(+) T lymphocytes are closely related with immune regulation after liver transplantation (LT). An additional factor which appears to play an important role with regard to transplantation immunity are exosomes, which are membrane-derived small vesicles released by various cells. However, the regulation of CD80(+) DCs derived exosomes on CD8(+) T cells in response to LT remains unclear. Methods: Ten LT patients and two donors were included in this study. Multiple immunofluorescence was per-formed to identify infiltrated CD8(+) T cells and DCs in human liver samples. The expression of NLRP3 and Ki-67 were measured using immunohistochemistry and immunofluorescence staining. Changes in CD80(+) DCs and CD8(+) T cells within the liver and blood of a mouse model of LT were detected with flow cytometry. After coculture with CD80(+) DCs derived exosomes, the proliferation, adhesion, and transmigration of CD8(+) T cells were determined with the use of CCK-8, Adhesion and Transmigration assay in vitro. CD8(+) T cells related cytokines were measured using Western blot, qRT-PCR and ELISA. Results: In human liver samples, there was an increase in intrahepatic CD8(+) T cell infiltration in the acute LT rejection group, an effect which was accompanied by high expressions of NLRP3 and Ki-67 index and a decrease in DCs. Similarly, lower levels of CD80(+) DCs were observed with acute rejection in an LT mouse model, along with increased numbers of CD8(+) T cells in the liver and blood. In vitro, CD80(+) DCs derived exosomes modulated the secretion of CD8(+) T cells from cytokines by down-regulating NLRP3 expression, combined with a synchro-nous inhibition in the adhesion, invasion, and proliferation of CD8(+) T cells. Conclusion: CD80(+) DCs derived exosomes negatively regulate CD8(+) T cells via inhibition of NLRP3 expression, a series of events which are essential to attenuate acute LT rejection. These results reveal a new role for CD80(+) DCs exosomes as related to tolerance induction in LT.
第一作者单位：[1]Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing 101100, China[2]Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing 101100, China[3]National Clinical Research Center for Digestive Diseases, Beijing 101100, China d Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 101100, China
通讯作者：
通讯机构：[1]Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing 101100, China[2]Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing 101100, China[3]National Clinical Research Center for Digestive Diseases, Beijing 101100, China d Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 101100, China[*1]No. 101 Lu Yuan Dong Road, Tong-Zhou District, Beijing 101100, China
推荐引用方式(GB/T 7714)：
Cui Bin,Sun Jie,Li Shi-Peng,et al.CD80(+) dendritic cell derived exosomes inhibit CD8(+) T cells through down-regulating NLRP3 expression after liver transplantation[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2022,109:doi:10.1016/j.intimp.2022.108787.
APA：
Cui Bin,Sun Jie,Li Shi-Peng,Zhou Guang-Peng,Chen Xiao-Jie...&Zhu Zhi-Jun.(2022).CD80(+) dendritic cell derived exosomes inhibit CD8(+) T cells through down-regulating NLRP3 expression after liver transplantation.INTERNATIONAL IMMUNOPHARMACOLOGY,109,
MLA：
Cui Bin,et al."CD80(+) dendritic cell derived exosomes inhibit CD8(+) T cells through down-regulating NLRP3 expression after liver transplantation".INTERNATIONAL IMMUNOPHARMACOLOGY 109.(2022)
