人间充质干细胞抑制单核细胞来源树突状细胞的分化和功能

deron

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主题：人间充质干细胞抑制单核细胞来源树突状细胞的分化和功能
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: C2 ^9 a6 w+ e9 M0 X& ^说明：原文来自Blood，干细胞之家新闻小组成员deron翻译（转帖请注明）
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( n! T; \9 r6 m间充质干细胞（MSCs）除了其多系分化能力外，在体外可以直接免疫抑制T细胞增殖。但是，它们是否也通过作用于第一步调节免疫系统仍不可知。在本研究中，我们着重处理了体外人MSCs对CD14+单核细胞来源树突状细胞（DCs）分化、成熟和功能性的影响。在粒/巨噬集落刺激因子（GM-CSF）和白介素4的诱导下，MSC共培养能够强烈抑制单核细胞向DCs的初始分化，只是这种作用是可逆的。此外，这种抑制在一个更高的MSC/单核细胞比率（1：10）下，无需细胞间接触。此外，MSCs处理后的成熟DCs显著减少了CD83的表达，表明了这些DC（在MSC处理后）偏向于未成熟状态。同时，我们也观察到提呈分子（HLA-DR和CD1a）和共刺激分子（CD80和CD86）表达降低和IL12分泌下调。相应的，MSC处理后成熟DCs对同种异源T细胞的同种异源刺激能力也受到损伤。总之，我们的数据首次证明了人MSCs能够抑制单核细胞向DCs（最强力的抗原提呈细胞）分化，从而显示出MSCs在顶级特异性免疫应答中的多种调节功能。- [7 M& p4 x: e; Q- t9 K
原摘要：Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, have a direct immunosuppressive effect on T-cell proliferation in vitro. However, it is unclear whether they also modulate the immune system by acting on the very first step. In this investigation, we addressed the effects of human MSCs on the differentiation, maturation, and function of dendritic cells (DCs) derived from CD14+ monocytes in vitro. Upon induction with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), MSC coculture could strongly inhibit the initial differentiation of monocytes to DCs, but this effect is reversible. In particular, such suppression could be recapitulated with no intercellular contact at a higher MSC/monocyte ratio (1:10). Furthermore, mature DCs treated with MSCs were significantly reduced in the expression of CD83, suggesting their skew to immature status. Meanwhile, decreased expression of presentation molecules (HLA-DR and CD1a) and costimulatory molecules (CD80 and CD86) and down-regulated IL-12 secretion were also observed. In consistence, the allostimulatory ability of MSC-treated mature DCs on allogeneic T cells was impaired. In conclusion, our data suggested for the first time that human MSCs could suppress monocyte differentiation into DCs, the most potent antigen-presenting cells (APCs), thus indicating the versatile regulation of MSCs on the ultimate specific immune response.0 K7 L* V9 ~0 n5 t
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原文：  

deron

回复 naturalkillerce 的帖子9 D0 D% o% z( |/ }8 w9 S8 A
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事实上，关于这个“ultimate specific immune response”与前文的逻辑关系，一直不得其解。想请教naturalkillerce兄“最终的免疫调节”，是个什么情况？