Toll样受体结合通过经干扰素贝塔和蛋白激酶R诱导的吲哚胺2，3加双氧酶1增强人骨髓来源

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主题：Toll样受体结合通过经干扰素贝塔和蛋白激酶R诱导的吲哚胺2，3加双氧酶1增强人骨髓来源间充质干细胞的免疫抑制特性/ q% t$ W% `# e1 C1 z

0 g$ x% g5 K" k: Z说明：原文来自Stem Cell，干细胞之家新闻小组成员deron翻译（转帖请注明）- |1 e0 @' V0 H3 n2 W

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间充质干细胞（MSC）在T细胞免疫方面具有独特的抑制特性，因而可作为一种有效手段用于治疗损伤性T细胞应答引发的相关疾病——如器官特异性自体免疫和移植物抗宿主病。Toll样受体（TLR）主要表达于抗原提呈细胞并识别保存的病原体来源组分。阻断TLR可以激活多种固有和适应性免疫应答途径，来消除和抵御侵入性病原体。本研究中，我们证明了人骨髓来源MSC表达的TLR增强了MSC的免疫抑制表型。TLR介导的免疫抑制反应不依赖于色氨酸代谢酶吲哚胺2，3加双氧酶1（IDO1）产生的免疫抑制物质犬尿氨酸。TLR诱导IDO1的反应涉及到一个自分泌的干扰素（IFN）β信号环，该信号环依赖于蛋白激酶R（PKR），并独立于IFNγ之外。这些数据赋予了TLR在MSC免疫生物学中一个新的角色，使得（生物体）在无IFNγ时增强MSC的免疫抑制特性，而非诱导促炎性免疫应答途径。PKR和IFNβ在促成MSC免疫抑制性物质犬尿氨酸的分泌上，发挥着之前未曾探明的重要作用。
1 _/ P+ p, g' j  b原摘要：Mesenchymal stem cells (MSC) display unique suppressive properties on T-cell immunity, thus representing an attractive vehicle for the treatment of conditions associated with harmful T-cell responses such as organ-specific autoimmunity and graft-versus-host disease. Toll-like receptors (TLR) are primarily expressed on antigen-presenting cells and recognize conserved pathogen-derived components. Ligation of TLR activates multiple innate and adaptive immune response pathways to eliminate and protect against invading pathogens. In this work, we show that TLR expressed on human bone marrow-derived MSC enhanced the immunosuppressive phenotype of MSC. Immunosuppression mediated by TLR was dependent on the production of immunosuppressive kynurenines by the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase-1 (IDO1). Induction of IDO1 by TLR involved an autocrine interferon (IFN)-β signaling loop, which was dependent on protein kinase R (PKR), but independent of IFN-γ. These data define a new role for TLR in MSC immunobiology, which is to augment the immunosuppressive properties of MSC in the absence of IFN-γ rather than inducing proinflammatory immune response pathways. PKR and IFN-β play a central, previously unidentified role in orchestrating the production of immunosuppressive kynurenines by MSC. ) R/ N+ }" N. @" Y

6 z( e5 g' G' u) |% s# f, D原文：+ E4 Q7 x' @, z( ~5 o

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作者认为,发挥主要作用的是TLR3和TLR4两种TLR，因为MSC和DC均表达TLR1-6，但是只有这两种受体在MSC中的表达高过DC。这种活化IDO的新的信号途径，需要活化的PKR、自分泌的IFNβ信号和活化的STAT1/IRF1

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回复 naturalkillerce 的帖子
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多谢naturalkillerce的详细指点。涉足免疫和信号通路的知识层次，直接影响到文献的理解和翻译深度。这一点您做得显然比我好，还望以后多多指点，互相交流！8 @: g, \) D5 X( j$ l
另外，关于GVHD（graft versus host disease）,在http://dict.bioon.com/search.asp ... %B8&matchtype=0中的翻译是“移植物抗宿主病”。平时我们研究临床相关的这一症状时，临床医生同样也称之为“移植物抗宿主病”。