The Potential Genes Mediate the Pathogenicity of Allogeneic CD4(+)T Cell in aGVHD Mouse Model.
The Potential Genes Mediate the Pathogenicity of Allogeneic CD4(+)T Cell in aGVHD Mouse Model.
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DOI：
10.1155/2021/9958745
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发表时间：
2021
影响因子：
--
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Yu Z;Qin C;Cao M;He X;Ren H;Liu H
急性移植物抗宿主病(AGVHD)是异基因造血干细胞移植(allo-HSCT)的严重并发症。由于aGVHD的发生，allo-HSCT较自体造血干细胞移植(Auto-HSCT)显著增加了死亡率。本研究建立了自体移植和异基因移植aGVHD小鼠模型，通过核糖核酸序列分析(RNA-Seq)检测不同组织中CD4+淋巴细胞的差异。对差异表达基因(Deg)进行聚类分析、功能注释和途径丰富分析。利用蛋白质相互作用(PPI)网络寻找HUB基因。MLR和细胞因子刺激可激活CD4+T细胞。用流式细胞分选机对细胞进行分类。所选基因通过qRT-PCR、组织学和免疫荧光染色进行了验证。使用GSE126518 GEO数据集验证HUB基因。浓缩分析揭示了在aGVHD中起重要作用的四条免疫相关途径，包括淋巴和非淋巴细胞之间的免疫调节相互作用，趋化因子受体结合趋化因子，细胞因子和细胞因子受体相互作用，以及趋化因子信号通路。同时，利用PPI网络确定了11个可能参与aGVHD免疫调节的新HUB基因，并通过qRT-PCR和GSE126518数据库进行了进一步验证。此外，CXCL7的蛋白表达水平与测序结果一致。综上所述，这项研究揭示了免疫调节相关的DEGS和途径在aGVHD的发病中起着至关重要的作用。这些发现可能为探讨aGVHD的发病机制和治疗提供新的线索。
Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). In this study, auto-HSCT and allo-HSCT aGVHD mouse models were built to detect the difference in CD4+ lymphocyte in different tissues based on ribonucleic acid sequencing (RNA-Seq) analysis. Clustering analysis, functional annotation, and pathway enrichment analysis were performed on differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to find hub genes. CD4+T cells were activated by MLR and cytokine stimulation. Cells were sorted out by a flow cell sorter. The selected genes were verified by qRT-PCR, histology, and immunofluorescence staining. The GSE126518 GEO dataset was used to verify the hub genes. Enrichment analysis revealed four immune-related pathways that play an important role in aGVHD, including immunoregulatory interactions between a lymphoid and a nonlymphoid cell, chemokine receptors binding chemokines, cytokine and cytokine receptor interaction, and the chemokine signaling pathway. At the same time, with the PPI network, 11 novel hub genes that were most likely to participate in immunoregulation in aGVHD were identified, which were further validated by qRT-PCR and the GSE126518 dataset. Besides, the protein expression level of Cxcl7 was consistent with the sequencing results. In summary, this study revealed that immunoregulation-related DEGs and pathways played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD.
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影响因子：
9.9
作者：
Snider J;Kotlyar M;Saraon P;Yao Z;Jurisica I;Stagljar I
通讯作者：
Stagljar I
影响因子：
7.3
作者：
Junttila IS
通讯作者：
Junttila IS
DOI：
10.1038/nri3212
发表时间：
2012-05-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Gaudin A;Tolar M;Peters OA
通讯作者：
Peters OA
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW