Cytosporone B (Csn-B), an NR4A1 agonist, attenuates acute cardiac allograft rejection by inducing differential apoptosis of CD4+T cells
Cytosporone B (Csn-B), an NR4A1 agonist, attenuates acute cardiac allograft rejection by inducing differential apoptosis of CD4+T cells
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Cytosporone B (Csn-B) 是一种 NR4A1 激动剂，通过诱导 CD4 T 细胞的差异性凋亡来减轻急性心脏同种异体移植排斥。
DOI：
10.1016/j.intimp.2022.108521
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发表时间：
2022
影响因子：
5.6
通讯作者：
Jiahong Xia
中科院分区：
文献类型：
--
作者：
Xiangchao Ding;Sheng Le;Ke Wang;Yunshu Su;Shanshan Chen;Chuangyan Wu;Jiuling Chen;Anchen Zhang;Jiahong Xia
CD 4 +T细胞介导的急性排斥反应是影响移植器官早期存活的主要因素。在这里，我们发现，核受体亚家族4 A组成员1（Nr 4A 1）上调心脏移植排斥反应，增加Nr 4A 1主要定位于移植物内浸润的CD 4 +T细胞。Nr 4A 1作为一种转录因子，在CD 4 +T细胞凋亡、分化和T细胞功能障碍中发挥重要作用，提示Nr 4A 1可能在移植排斥反应中发挥重要作用。细胞孢素B（Csn-B）是一种天然存在的Nr 4 A1激动剂，Csn-B在心脏排斥反应的生理过程中的作用尚不清楚。本研究建立了小鼠腹腔异位心脏移植急性排斥反应模型，探讨Csn-B是否能通过调节CD 4 +T淋巴细胞反应减轻移植急性排斥反应。结果表明，Csn-B延长小鼠心脏移植物的存活和减少同种异体移植物中的炎症。随后，证实Csn-B通过诱导非Treg细胞凋亡和促进Treg细胞分化发挥作用。最后，我们还证实了Csn-B通过直接靶向CD 4 +T细胞中的Nr 4A 1来减弱急性排斥反应。我们的数据表明，Csn-B是一种有前途的新的心脏移植急性排斥反应的治疗方法。
CD4+T cell-mediated acute rejection remains a major factor that affects the early survival of transplanted organs post-transplantation. Here, we reveal that nuclear receptor subfamily 4 Group A member 1 (Nr4A1) was upregulated during cardiac allograft rejection and that the increased Nr4A1 was primarily localized in intragraft-infiltrating CD4+T cells. Nr4A1 acts as a transcription factor with an important role in CD4+T cell apoptosis, differentiation and T cell dysfunction, which indicates that Nr4A1 may play a critical role in transplant rejection. Cytosporone B (Csn-B) is a naturally occurring agonist of Nr4A1, and the role of Csn-B in the physiological process of cardiac rejection is poorly defined. This study constructed an acute rejection model of abdominal heterotopic cardiac transplantation in mice and investigated whether Csn-B could attenuate acute transplant rejection by modulating the CD4+T lymphocyte response. The results showed that Csn-B prolonged murine cardiac allograft survival and reduced inflammation in allografts. Subsequently, it was confirmed that Csn-B functions by inducing non-Treg apoptosis and promoting Treg cell differentiation. Finally, we also confirmed that Csn-B attenuates acute rejection by directly targeting Nr4A1 in CD4+T cells. Our data suggest that Csn-B is a promising novel therapeutic approach for acute cardiac allograft rejection.