c-Rel is an essential transcription factor for the development of acute graft-versus-host disease in mice.
c-Rel is an essential transcription factor for the development of acute graft-versus-host disease in mice.
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DOI：
10.1002/eji.201243282
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发表时间：
2013-09
影响因子：
5.4
通讯作者：
Yu, Xue-Zhong
中科院分区：
文献类型：
--
作者：
Yu, Yu;Wang, Dapeng;Kaosaard, Kane;Liu, Chen;Fu, Jianing;Haarberg, Kelley;Anasetti, Claudio;Beg, Amer A.;Yu, Xue-Zhong
已知Rel/NF-κB家族的转录因子在免疫和炎症中发挥不同的作用，尽管c-Rel在移植耐受和GVHD中的假定作用仍然不清楚。我们在这里报告说，T细胞缺乏c-Rel有一个显着降低的能力，导致急性移植物抗宿主病（GVHD）异基因骨髓移植（BMT）后，使用主要和次要的组织相容性不匹配的小鼠模型。在了解潜在机制的研究中，我们发现c-Rel-/- T细胞在异基因受体中淋巴器官中扩增和浸润GVHD靶器官的能力降低。c-Rel-/- T细胞在遇到同种异体抗原后不能分化为Th 1细胞，但在向Foxp 3+调节性T细胞（TcR）的分化中增强。此外，c-Rel-/- T细胞在很大程度上保留了介导移植物抗白血病（GVL）反应的活性。综上所述，我们的研究结果表明，c-Rel在T细胞中在急性GVHD的诱导中起着重要作用，并表明c-Rel可以成为临床上同种异体HCT治疗干预的潜在靶点。
Transcription factor of the Rel/NF-κB family are known to play different roles in immunity and inflammation, although the putative role of c-Rel in transplant tolerance and GVHD remains elusive. We report here that T cells deficient for c-Rel have a dramatically reduced ability to cause acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) using major and minor histocompatibility mismatched murine models. In the study to understand the underlying mechanisms, we found that c-Rel-/- T cells had reduced ability to expand in lymphoid organs and to infiltrate in GVHD target organs in allogeneic recipients. c-Rel-/- T cells were defective in the differentiation into Th1 cells after encountering alloantigens, but were enhanced in the differentiation towards Foxp3+ regulatory T cells (Tregs). Furthermore, c-Rel-/- T cells had largely preserved activity to mediate graft-versus leukemia (GVL) response. Taken together, our findings indicate that c-Rel plays an essential role in T cells in the induction of acute GVHD, and suggest that c-Rel can be a potential target for therapeutic intervention in allogeneic HCT in clinic.
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DOI：
10.1111/j.1600-6143.2008.02533.x
发表时间：
2009-03
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
O'Shaughnessy MJ;Vogtenhuber C;Sun K;Sitcheran R;Baldwin AS;Murphy WJ;Dang L;Jaffee B;Palmer E;Serody JS;Blazar BR
通讯作者：
Blazar BR
影响因子：
10.5
作者：
KONTGEN, F;GRUMONT, RJ;GERONDAKIS, S
通讯作者：
GERONDAKIS, S
影响因子：
2.6
作者：
Meignin, W;de Latour, RP;Socié, G
通讯作者：
Socié, G
影响因子：
4.3
作者：
Iclozan, Cristina;Yu, Yu;Liu, Chen;Liang, Yaming;Yi, Tangsheng;Anasetti, Claudio;Yu, Xue-Zhong
通讯作者：
Yu, Xue-Zhong
影响因子：
15.9
作者：
Hilliard, BA;Mason, N;Chen, YH
通讯作者：
Chen, YH