CCR7 expressing mesenchymal stem cells potently inhibit graft-versus-host disease by spoiling the fourth supplemental Billingham's tenet.
CCR7 expressing mesenchymal stem cells potently inhibit graft-versus-host disease by spoiling the fourth supplemental Billingham's tenet.
复制标题
表达 CCR7 的间充质干细胞通过破坏第四个补充 Billingham 的原则来有效抑制移植物抗宿主病
DOI：
10.1371/journal.pone.0115720
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li H;Jiang YM;Sun YF;Li P;Dang RJ;Ning HM;Li YH;Zhang YJ;Jiang XX;Guo XM;Wen N;Han Y;Mao N;Chen H;Zhang Y
急性移植物抗宿主病（GvHD）的临床治疗间充质干细胞（MSCs）并不像预期的那样令人满意。次级淋巴器官（slo）是启动免疫反应或诱导耐受的主要生态位。我们之前的研究表明，CCR7引导小鼠MSC细胞系C3H10T1/2向slo迁移。本研究采用慢病毒转染系统（MSCs/CCR7）将CCR7基因转染到小鼠间充质干细胞中。进一步研究MSCs/CCR7的免疫调节机制。在炎症细胞因子的刺激下，MSCs/CCR7增加了一氧化氮的分泌，并在体外平息了T细胞的免疫反应。免疫荧光染色结果显示，输注的MSCs/CCR7能够在体内迁移到slo内适当的T细胞富集区并重新定位。与正常MSCs相比，MSCs/CCR7在延长GvHD小鼠生存期和减轻临床评分方面表现出更强的作用。由于关键的重定位位点，MSCs/CCR7共输注有效地使slo中的T细胞更像naïve，从而控制T细胞从slo到靶器官的运输。通过破坏Billingham的第四个补充原则，MSCs/CCR7有效地抑制了GvHD的发展。本研究为MSCs/CCR7低剂量输注提供了一种新的治疗策略，为临床免疫疾病的治疗提供了强有力的免疫调节作用。
The clinical acute graft-versus-host disease (GvHD)-therapy of mesenchymal stem cells (MSCs) is not as satisfactory as expected. Secondary lymphoid organs (SLOs) are the major niches serve to initiate immune responses or induce tolerance. Our previous study showed that CCR7 guide murine MSC line C3H10T1/2 migrating to SLOs. In this study, CCR7 gene was engineered into murine MSCs by lentivirus transfection system (MSCs/CCR7). The immunomodulatory mechanism of MSCs/CCR7 was further investigated. Provoked by inflammatory cytokines, MSCs/CCR7 increased the secretion of nitric oxide and calmed down the T cell immune response in vitro. Immunofluorescent staining results showed that transfused MSCs/CCR7 can migrate to and relocate at the appropriate T cell-rich zones within SLOs in vivo. MSCs/CCR7 displayed enhanced effect in prolonging the survival and alleviating the clinical scores of the GvHD mice than normal MSCs. Owing to the critical relocation sites, MSCs/CCR7 co-infusion potently made the T cells in SLOs more naïve like, thus control T cells trafficking from SLOs to the target organs. Through spoiling the fourth supplemental Billingham’s tenet, MSCs/CCR7 potently inhibited the development of GvHD. The study here provides a novel therapeutic strategy of MSCs/CCR7 infusion at a low dosage to give potent immunomodulatory effect for clinical immune disease therapy.
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影响因子：
12.4
作者：
通讯作者：
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影响因子：
7.3
作者：
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通讯作者：
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
20.3
作者：
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通讯作者：
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