人骨髓基质细胞通过吲哚胺2，3加双氧酶介导的色氨酸下调抑制同种异基因T细胞应答

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主题：人骨髓基质细胞通过吲哚胺2，3加双氧酶介导的色氨酸下调抑制同种异基因T细胞应答1 s7 i2 P1 n' `8 v7 ?/ y
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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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6 [6 w: F, p& J  }: V骨髓间充质干细胞（MSCs）可以抑制同种异基因T细胞应答，然而MSC介导这种免疫抑制反应的作用机制尚有争议。最近，（研究者）发现吲哚胺2，3加双氧酶（IDO）通过T细胞抑制效应作用于专职抗原提呈细胞。IDO由干扰素γ诱导生成并可促使色氨酸转化成犬尿氨酸。本文我们证明了人MSC表达IDO蛋白且在IFNγ刺激后呈现IDO活性。MSCs在混合淋巴细胞反应（MLRs）中抑制同种异基因T细胞应答。同时，我们检测MSC/MLR共培养上清发现，IDO的活化作用导致色氨酸消耗和犬尿氨酸积累。色氨酸的加入显著恢复了同种异基因T细胞的增殖，因而IDO介导的色氨酸异化作用成为人MSCs抑制T细胞的一种新的作用机制。由于IDO介导的T细胞抑制作用依赖于MSC活化，因而IDO活性的调制可能改变不同治疗应用中MSC的免疫调节特性。" }) v2 d" O3 x4 j3 p, {  D4 D, n
原摘要：Marrow stromal cells (MSCs) inhibit allogeneic T-cell responses, yet the molecular mechanism mediating this immunosuppressive effect of MSCs remains controversial. Recently, expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-gamma (IFN-gamma) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in professional antigen-presenting cells. Here we show that human MSCs express IDO protein and exhibit functional IDO activity upon stimulation with IFN-gamma. MSCs inhibit allogeneic T-cell responses in mixed lymphocyte reactions (MLRs). Concomitantly, IDO activity resulting in tryptophan depletion and kynurenine production is detected in MSC/MLR coculture supernatants. Addition of tryptophan significantly restores allogeneic T-cell proliferation, thus identifying IDO-mediated tryptophan catabolism as a novel T-cell inhibitory effector mechanism in human MSCs. As IDO-mediated T-cell inhibition depends on MSC activation, modulation of IDO activity might alter the immunosuppressive properties of MSCs in different therapeutic applications.
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