Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation.
Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation.
复制标题
来氟米特通过抑制适应性免疫细胞反应和 NF-κB 信号激活来抑制大鼠对小鼠心脏异种移植排斥
DOI：
10.1177/09636897211054503
复制
发表时间：
2021-01
影响因子：
3.3
通讯作者：
Qi Z
中科院分区：
文献类型：
--
作者：
Ma Y;Xie B;Guo J;Chen Y;Zhong M;Lin Q;Hua J;Zhong J;Luo X;Yan G;Dai H;Qi Z
异种移植是解决人类供体器官和组织严重短缺的一个潜在解决方案。人源化动物模型的产生减弱了强先天免疫反应，如补体介导的超急性排斥反应。然而，急性血管排斥反应和细胞介导的排斥反应仍然是异种移植的主要障碍，这限制了异种移植的临床应用。在这项研究中，我们使用大鼠对小鼠心脏异种移植模型系统地研究了LEF的免疫抑制作用。将SD大鼠异种心脏移植到C57BL/6小鼠体内，经LEF处理后存活34.5 d。相比之下，BALB/c异体心脏移植到C57BL/6小鼠体内，经LEF治疗后存活31天。与生理盐水治疗相比，LEF治疗降低了受体脾细胞中的异种反应性T细胞和CD19+ B细胞。最重要的是，LEF处理通过减少移植物中异种反应性T细胞和B细胞浸润、炎症基因表达和IgM沉积来保护心肌细胞。体内实验表明，LEF治疗通过抑制NF-κB信号通路的激活来消除异种反应性和同种异体反应性T淋巴细胞和B淋巴细胞。综上所述，这些观察结果补充了支持LEF在异种移植中的潜在应用的证据。
Xenotransplantation is a potential solution for the severe shortage of human donor organs and tissues. The generation of humanized animal models attenuates strong innate immune responses, such as complement-mediated hyperacute rejection. However, acute vascular rejection and cell mediated rejection remain primary barriers to xenotransplantation, which limits its clinical application. In this study, we systematically investigated the immunosuppressive effect of LEF using a rat-to-mouse heart xenotransplantation model. SD rat xenogeneic hearts were transplanted into C57BL/6 mice, and survived 34.5 days after LEF treatment. In contrast, BALB/c allogeneic hearts were transplanted into C57BL/6 mice, and survived 31 days after LEF treatment. Compared to normal saline treatment, LEF treatment decreased xenoreactive T cells and CD19+ B cells in recipient splenocytes. Most importantly, LEF treatment protected myocardial cells by decreasing xenoreactive T and B cell infiltration, inflammatory gene expression, and IgM deposition in grafts. In vivo assays revealed that LEF treatment eliminated xenoreactive and alloreactive T and B lymphocytes by suppressing the activation of the NF-κB signaling pathway. Taken together, these observations complement the evidence supporting the potential use of LEF in xenotransplantation.
登录
查看更多内容
影响因子：
3.5
作者：
MATTAR, T;KOCHHAR, K;FINNEGAN, A
通讯作者：
FINNEGAN, A
影响因子：
6.2
作者：
Siemasko, KF;Chong, ASF;Finnegan, A
通讯作者：
Finnegan, A
影响因子：
5
作者：
Dai, Chen;Lu, Fang-Na;Qi, Zhong-Quan
通讯作者：
Qi, Zhong-Quan
影响因子：
3.4
作者：
Li, Bing;Tian, Lihua;Wang, Xuefeng
通讯作者：
Wang, Xuefeng
影响因子：
56.9
作者：
BACH, FH;VOYNOW, NK
通讯作者：
VOYNOW, NK