Gene-expression profiles of peripheral blood mononuclear cell subpopulations in acute graft-vs-host disease following cord blood transplantation
Gene-expression profiles of peripheral blood mononuclear cell subpopulations in acute graft-vs-host disease following cord blood transplantation
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DOI：
10.1016/j.exphem.2008.07.007
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发表时间：
2008-12-01
影响因子：
2.6
通讯作者：
Tojo, Arinobu
中科院分区：
文献类型：
--
作者：
Takahashi, Naoyuki;Sato, Noriharu;Tojo, Arinobu
客观的。与其他来源的同种异体造血干细胞移植相比，尽管使用人类白细胞抗原错配较多的同种异体干细胞，但脐带血（CB）移植（CBT）在急性移植物抗宿主病（GVHD）的发生率和严重程度方面具有临床优势。然而，CBT 后发生的急性 GVHD 的详细病理生理学尚未阐明。在本研究中，我们旨在阐明CBT后急性GVHD的分子机制。材料和方法。我们对外周血母细胞 (PBMC) 的四个亚群（CD4(+)、CD8(+)、CD14(+) 和 CD56(+)）中的每一个进行了免疫调节基因的微阵列表达谱分析，这些细胞取自 8 名在无关 CBT 后患有急性 GVHD 的血液恶性肿瘤患者。结果。我们鉴定了 55 个基因，这些基因在急性 GVHD 期间与恢复期相比有差异表达。其中，22个在多个PBMC亚群中同时表现出差异表达。特别是，在急性 GVHD 期间，四个亚群中的至少三个亚群中，五个基因（TNFSF10/TRAIL、IL1RN、IFI27、GZMB 和 CCR5）上调，三个基因（CLK1、TNFAIP3 和 BTG1）下调。此外，TNFAIP3、KLF2、ZFP36和BTG1等抗炎因子的下调似乎与免疫反应加速有关，从而加剧急性GVHD。同时，CCL5、TNFAIP3、KLRB1/CD161、BY55/CD160和PTGS2/COX2等几个基因的差异表达可能受到CB来源细胞发育不成熟的影响。结论。这些结果将有助于了解 CBT 后急性 GVHD 期间炎症细胞行为的分子机制。 (C) 2008 ISEH - 血液学和干细胞学会。由爱思唯尔公司出版
Objective. Compared with allogeneic hematopoietic stem cell transplantation using other sources, cord blood (CB) transplantation (CBT) has clinical advantages in terms of incidence and severity of acute graft-vs-host disease (GVHD), despite using allogeneic stem cells with more human leukocyte antigen mismatches. However, detailed pathophysiology of acute GVHD developed after CBT has not yet been elucidated. In this study, we aimed to clarify the molecular mechanism of acute GVHD after CBT.Materials and Methods. We performed microarray expression profiling of immunoregulatory genes on each of four subpopulations (CD4(+), CD8(+), CD14(+), and CD56(+)) of peripheral blood mommuclear cells (PBMCs), which were taken from eight patients with hematologic malignancies who suffered from acute GVHD after unrelated CBT.Results. We identified 55 genes, which were differentially expressed during acute GVHD compared to recovery phase. Among them, 22 showed differential expression concurrently in multiple PBMC subpopulations. In particular, five genes (TNFSF10/TRAIL, IL1RN, IFI27, GZMB, and CCR5) were upregulated and three genes (CLK1, TNFAIP3 and BTG1) were downregulated in at least three out of four subpopulations during acute GVHD. In addition, downregulation of antiinflammatory factors, such as TNFAIP3, KLF2, ZFP36, and BTG1, seems to be involved in acceleration of immune response, thus exacerbation of acute GVHD. Meanwhile, differential expression of several genes, such as CCL5, TNFAIP3, KLRB1/CD161, BY55/CD160, and PTGS2/COX2, was assumedly affected by the developmental immaturity of CB-derived cells.Conclusions. These results will contribute to the understanding of molecular mechanism underlying the behavior of inflammatory cells during acute GVHD following CBT. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.