Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle
Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle
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DOI：
10.1097/01.tp.0000244572.24780.54
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发表时间：
2007-01-15
期刊：
影响因子：
6.2
通讯作者：
Dazzi, Francesco
中科院分区：
文献类型：
--
作者：
Ramasamy, Rajesh;Fazekasova, Henrietta;Dazzi, Francesco
背景资料。间充质干细胞(MSCs)在造血发育中起着至关重要的作用，并被证明具有强大的免疫抑制作用。本研究探讨骨髓间充质干细胞对外周血单核细胞向树突状细胞分化和功能的影响。取正常骨髓来源的人骨髓间充质干细胞，在体外用粒细胞-巨噬细胞集落刺激因子和白介素4刺激外周血单核细胞，形成DC。然后检测单核细胞DC特有的标志物的表达及其刺激同种异体T细胞的能力。此外，通过流式细胞仪分析和免疫印迹分析MSCs对单核细胞来源的DC细胞周期和各种细胞周期蛋白表达的影响。MSCs阻断单核细胞向DC的分化，降低其抗原提呈能力。这是由于一组单核细胞进入细胞周期的G(1)期，在G(O)期积累了逐渐数量的细胞。细胞周期蛋白D2表达下调。然而，与在MSCs存在的刺激下观察到的T细胞不同，p27(Kip1)的表达被发现降低，这表明参与了相似但不相同的途径。我们得出结论，MSCs通过干扰细胞周期而损害单核细胞的分化和功能。这些发现表明，MSC诱导的免疫抑制可能是更普遍的抗增殖作用的副产品。
Background. Mesenchymal stem cells (MSCs) play a crucial role in hematopoietic development and have been shown to exert a powerful immunosuppressive effect. In this study, we investigated the effect of bone marrow MSC on the differentiation and function of peripheral blood monocytes into dendritic cells (DCs).Methods. Human MSCs, generated from normal bone marrow, were added to peripheral blood monocytes stimulated in vitro with granulocyte-macrophage colony stimulating factor and interleukin-4 to become DCs. Monocytes were then examined for the expression of markers characteristic of DCs and their ability to stimulate allogeneic T cells. In addition, the effect of MSCs on the cell cycle of monocyte -derived DCs and the expression of various cell cycle proteins were analyzed by cytometric analysis and Western blotting with specific antibodies.Results. MSCs blocked the differentiation of monocytes into DCs and impaired their antigen- presenting ability. This resulted from a block of monocytes from entering the G(1) phase of the cell cycle with a progressive number of cells accumulating in the G(o) phase. Cyclin D2 was downregulated. However, differently from what was observed in T-cells stimulated in the presence of MSCs, the expression of p27(kip1) was found decreased, suggesting the involvement of similar but not identical pathways.Conclusions. We conclude that MSCs impair monocyte differentiation and function by interfering with the cell cycle. These findings imply that MSC-induced immunosuppression might be a side product of a more general antiproliferative effect.