Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells
Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells
复制标题
DOI：
10.4049/jimmunol.177.4.2080
复制
发表时间：
2006-08-15
影响因子：
4.4
通讯作者：
Fibbe, Willem E.
中科院分区：
文献类型：
--
作者：
Nauta, Alma J.;Kruisselbrink, Alwine B.;Fibbe, Willem E.
间充质干细胞(MSCs)不仅能够逃避免疫系统，而且已被证明对T细胞增殖具有深刻的免疫抑制作用。然而，它们对免疫反应的启动者树突状细胞(DC)的影响相对未知。本研究探讨人骨髓间充质干细胞对CD34(+)来源的DC和单核细胞来源的DC分化和功能的影响。在分化过程中，MSCs的存在阻断了CD14(+)CD1a(-)前体细胞向真皮/间质DC的分化，但不影响CD1a(+)朗格汉斯细胞的产生。与这些观察结果一致，MSCs也完全阻止了单核细胞产生未成熟的DC。MSCs对DC分化的抑制作用呈剂量依赖关系，并导致表型和功能的改变，表现为共刺激分子的表达减少和刺激初始T细胞增殖的能力受阻。MSCs的抑制作用是通过可溶性因子介导的。综上所述，MSCs对CD34(+)来源的DC和单核细胞来源的DC的生成和功能均有明显的抑制作用，仅次于T细胞的抗增殖作用，表明MSCs能够在多个水平上调节免疫反应。
Mesenchymal stem cells (MSCs) are not only able to evade the immune system, but they have also been demonstrated to exert profound immunosuppressive properties on T cell proliferation. However, their effect on the initiators of the immune response, the dendritic cells (DCs), are relatively unknown. In the present study, the effects of human MSCs on the differentiation and function of both CD34(+)-derived DCs and monocyte-derived DCs were investigated. The presence of MSCs during differentiation blocked the differentiation of CD14(+)CD1a(-) precursors into dermat/interstitial DCs, without affecting the generation of CD1a(+) Langerhans cells. In line with these observations, MSCs also completely prevented the generation of immature DCs from monocytes. The inhibitory effect of MSCs on DC differentiation was dose dependent and resulted in both phenotypical and functional modifications, as demonstrated by a reduced expression of costimulatory molecules and hampered capacity to stimulate naive T cell proliferation. The inhibitory effect of MSCs was mediated via soluble factors. Taken together, these data demonstrate that MSCs, next to the antiproliferative effect on T cells, have a profound inhibitory effect on the generation and function of both CD34(+)-derived and monocyte-derived DCs, indicating that MSCs are able to modulate immune responses at multiple levels.