The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease.
The role of programmed cell death ligand-1 (PD-L1/CD274) in the development of graft versus host disease.
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DOI：
10.1371/journal.pone.0060367
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Moshfegh A
中科院分区：
文献类型：
--
作者：
Al-Chaqmaqchi H;Sadeghi B;Abedi-Valugerdi M;Al-Hashmi S;Fares M;Kuiper R;Lundahl J;Hassan M;Moshfegh A
程序性细胞死亡配体-1(PD-L1/CD274)是一种免疫调节分子，参与了肿瘤和骨髓移植的并发症，如移植物排斥反应和移植物抗宿主病。本研究旨在评估造血干细胞移植后这种分子的动态表达与急性移植物抗宿主病的关系。将雌性BALB/c小鼠用丁硫丹和环磷酰胺处理后，分别移植同基因或异基因(雄性C57BL/6小鼠)骨髓和脾细胞。用定量聚合酶链式反应、免疫印迹和免疫组织化学方法检测PD-L1在不同时间点的表达。在移植后第5天和第7天，同种异体但非同基因移植动物的肌肉和肾脏中PD-L1的表达显著上调，但肝脏中PD-L1的表达没有明显上调。在移植异基因骨髓细胞的小鼠中，PD-L1的表达增强与相应时间段血清干扰素γ和肿瘤坏死因子α水平的升高有关。我们的研究结果表明，异基因移植后PD-L1的诱导和表达与同基因移植后不同，并且在急性移植物抗宿主病的早期阶段，PD-L1有利于靶器官而不是非靶器官。这是首次将PD-L1在基因、蛋白质和活性水平上的动态与急性移植物抗宿主病的早期发展联系起来的研究。我们的结果提示，PD-L1在肌肉和肾脏(非靶组织)中的高表达在急性移植物抗宿主病中对骨骼肌起到保护作用。
Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease.
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影响因子：
4.8
作者：
Sadeghi, B.;Aghdami, N.;Hassan, M.
通讯作者：
Hassan, M.
影响因子：
6.2
作者：
Schilbach, Karin;Schick, Judith;Eyrich, Matthias
通讯作者：
Eyrich, Matthias
PD-L1的组织表达介导外周T细胞耐受性。
影响因子：
15.3
作者：
Keir, ME;Liang, SC;Guleria, I;Latchman, YE;Qipo, A;Albacker, LA;Koulmanda, M;Freeman, GJ;Sayegh, MH;Sharpe, AH
通讯作者：
Sharpe, AH
影响因子：
20.3
作者：
Mielcarek, M;Martin, PJ;Storb, R
通讯作者：
Storb, R
影响因子：
168.9
作者：
Ferrara, James L. M.;Levine, John E.;Reddy, Pavan;Holler, Ernst
通讯作者：
Holler, Ernst