The inhibition of T-cells proliferation by mouse mesenchymal stem cells through the induction of p16INK4A-cyclin D1/cdk4 and p21waf1, p27kip1-cyclin E/cdk2 pathways
The inhibition of T-cells proliferation by mouse mesenchymal stem cells through the induction of p16INK4A-cyclin D1/cdk4 and p21waf1, p27kip1-cyclin E/cdk2 pathways
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DOI：
10.1016/j.cellimm.2007.03.003
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发表时间：
2007-01-01
影响因子：
4.3
通讯作者：
Kim, Chun-Choo
中科院分区：
文献类型：
--
作者：
Kim, Jeong-A;Hong, Sungyoul;Kim, Chun-Choo
间充质干细胞（MSC）已被证明下调T细胞反应。然而，其机制仍然未知。在本研究中，我们报道了BALB/c骨髓来源的MSC在混合淋巴细胞反应（MLR）中抑制同种异体T细胞的增殖，这种抑制依赖于细胞-细胞接触，并且不诱导凋亡。此外，细胞周期分析表明，T细胞，在MSC的存在下，被阻止在G 0/G1期通过。通过p16（INK 4A）-cyclin DI/cdk 4复合物和p21（waf 1）、p27（kip 1）-cyclin E/cdk 2复合物途径阻断视网膜母细胞瘤蛋白（Rb）的磷酸化。我们的研究结果表明，骨髓间充质干细胞可以通过直接调节活化T细胞的克隆扩增，在维持免疫稳态中发挥重要作用。MSC表现出的新的T细胞调节机制可能在各种治疗应用中证明是有用的。(c)2007年由Elsevier Inc.出版
Mesenchymal stem cells (MSCs) have been shown to down-regulate T-cell responses. However, the mechanisms underlying remain unknown. In this study, we report that BALB/c bone marrow-derived MSCs inhibit the proliferation of allogeneic T-cells in mixed lymphocyte reactions (MLR), This inhibition is dependent on cell-cell contact, and do not induce apoptosis. Furthermore, cell-cycle analyses reveal that T-cells, in the presence of MSCs, are arrested in the G0/G1 phase through. The blockage of phosphorylation of retinoblastoma protein (Rb), mediated by the p16(INK4A)-cyclin DI/cdk4 complex and p21(waf1), p27(kip1)-cyclin E/cdk2 complex pathway. Our results suggest that MSCs may perform a crucial function in the maintenance of immune homeostasis, via direct regulation of the clonal expansion of activated T-cells. The novel T-cell regulatory mechanism exhibited by MSCs may prove useful in a variety of therapeutic applications. (c) 2007 Published by Elsevier Inc.