Bone Marrow-Derived Mesenchymal Stem Cells Favor the Immunosuppressive T Cells Skewing in a Helicobacter Pylori Model of Gastric Cancer
Bone Marrow-Derived Mesenchymal Stem Cells Favor the Immunosuppressive T Cells Skewing in a Helicobacter Pylori Model of Gastric Cancer
复制标题
骨髓间充质干细胞在幽门螺杆菌胃癌模型中偏向于免疫抑制 T 细胞
DOI：
10.1089/scd.2013.0166
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发表时间：
2013-11-01
影响因子：
4
通讯作者：
Hou, Xiaohua
中科院分区：
文献类型：
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作者：
Lin, Rong;Ma, Huan;Hou, Xiaohua
骨髓间充质干细胞（BM-MSCs）在幽门螺杆菌诱导的胃癌发生中起重要作用。虽然机制还不清楚，但BM-MSC已被证明有助于在许多疾病中发现的免疫抑制反应。在这里，将BM-MSCs移植到小鼠的胃中，小鼠适应了44周的H。幽门感染在移植后第28天，BM-MSCs从浆膜下迁移到胃粘膜层。移植的BM-MSCs显著刺激全身和局部分泌白细胞介素-10（IL-10）的T细胞和调节性T细胞（Treg）功能。这一观察结果与脾脏单个核细胞中CD 4（+）IL-10（+）细胞和CD 4（+）CD 25（+）FoxP 3（+）细胞的百分比增加相关。未接受BM-MSC的幽门螺杆菌感染小鼠。此外，抑制性细胞因子IL-10和转化生长因子-1在胃组织中增加，而炎性干扰素-（IFN-）减少。BM-MSC移植小鼠也出现了升高的IL-10/IFN分泌和Treg/Th 17比率。同时建立了BM-MSCs存在或不存在的共培养体系，以评价体外免疫应答。观察到分泌IL-10的T细胞和TcB的增加，与加塔-3和FoxP 3的表达增加、上清液中IL-10的产生以及胃上皮细胞（GEC）的增殖相关。这些结果表明，骨髓间充质干细胞移植到慢性H。幽门螺杆菌感染的小鼠模型导致免疫抑制环境的产生。骨髓间充质干细胞介导的局部和全身免疫抑制可能有助于与H.幽门诱发胃癌
Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in Helicobacter pylori-induced gastric carcinogenesis. While the mechanism is not well understood, BM-MSCs have been shown to contribute to the immunosuppressive response found in a number of diseases. Here, BM-MSCs were transplanted into the stomach of mice with a 44-week mouse-adapted H. pylori infection. At day 28 post-transplantation, BM-MSCs migrated from the subserosal to the mucosal layer of the stomach. The grafted BM-MSCs significantly stimulated systemic and local interleukin-10 (IL-10)-secreting T cell and regulatory T cell (Treg) functions. This observation was correlated with an increased percentage of CD4(+)IL-10(+) cells and CD4(+)CD25(+)FoxP3(+) cells in splenic mononuclear cells compared with H. pylori-infected mice not receiving BM-MSCs. Moreover, inhibitory cytokines IL-10 and transforming growth factor-1 increased in the gastric tissue, while there was a decrease in inflammatory interferon- (IFN-). BM-MSC-transplanted mice also developed elevated IL-10/IFN- secreting and Treg/Th17 ratios. A coculture system in the presence or absence of BM-MSCs was also established to evaluate the immune responses in vitro. An increase in IL-10-secreting T cells and Tregs, associated with increased expression of Gata-3 and FoxP3, generation of IL-10 in the supernatant, and proliferation of gastric epithelial cells (GECs) was observed. These findings demonstrate that transplantation of BM-MSCs into a chronic H. pylori-infected mouse model results in the generation of an immunosuppressive environment. The local and systemic immunosuppression mediated by BM-MSCs likely contributed to an environment that is compatible with the development of H. pylori-induced gastric cancer.