ZBTB20 通过 NFкB 介导的炎症反应调节小鼠心脏移植中的同种异体排斥反应。

ZBTB20 regulates cardiac allograft rejection through NFкB-mediated inflammation in mouse heart transplantation.

机构信息

Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macao SAR, China.

出版信息

Transpl Immunol. 2022 Oct;74:101676. doi: 10.1016/j.trim.2022.101676. Epub 2022 Jul 22.

DOI:10.1016/j.trim.2022.101676

PMID:35872083

Abstract

Allograft rejection is a major obstacle for the long-term survival of heart transplantation (Htx) patients. The cardiac allograft rejection requires the activation of macrophages and effector T cells. In this study, we explored the role of zinc-finger and BTB domain containing protein 20 (ZBTB20) in the regulation of heart allograft rejection. Flow cytometry analysis of the spleen cells from mice undergoing an acute cardiac rejection revealed that the ZBTB20 protein expression was upregulated in both T and B cells(n = 4，P < 0.01). In addition, ZBTB20 gene knockdown significantly prolonged the survival of heart allografts in mice(n = 4，P < 0.01). Lack of ZBTB20 increased the expression of Foxp3 and limited the response of T helper 1 (Th1) cells(n = 4，P < 0.01). The ZBTB20-related regulation occurred through the activation of the NFкB pathway. In conclusion, our data suggest that ZBTB20 is involved in the regulation of T cells involved in acute heart allograft rejection. Hence, downregulation of ZBTB20 expression may inhibit T cells to prolong heart transplant survival.

摘要

同种异体移植排斥反应是心脏移植（Htx）患者长期存活的主要障碍。心脏同种异体移植排斥反应需要激活巨噬细胞和效应 T 细胞。在这项研究中，我们探讨了锌指和 BTB 结构域蛋白 20（ZBTB20）在调节心脏同种异体移植排斥反应中的作用。对发生急性心脏排斥反应的小鼠脾细胞进行流式细胞术分析显示，ZBTB20 蛋白在 T 和 B 细胞中均上调（n=4，P<0.01）。此外，ZBTB20 基因敲低显著延长了心脏同种异体移植物在小鼠中的存活时间（n=4，P<0.01）。缺乏 ZBTB20 增加了 Foxp3 的表达，并限制了 T 辅助 1（Th1）细胞的反应（n=4，P<0.01）。ZBTB20 相关的调节是通过 NFкB 途径的激活发生的。总之，我们的数据表明 ZBTB20 参与了调节急性心脏同种异体移植排斥反应中的 T 细胞。因此，下调 ZBTB20 的表达可能抑制 T 细胞，从而延长心脏移植的存活时间。