Monocytic MDSCs regulate macrophage-mediated xenogenic cytotoxicity
Monocytic MDSCs regulate macrophage-mediated xenogenic cytotoxicity
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DOI：
10.1016/j.trim.2015.07.002
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发表时间：
2015-10-01
影响因子：
1.5
通讯作者：
Miyagawa, Shuji
中科院分区：
文献类型：
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作者：
Maeda, Akira;Eguchi, Hiroshi;Miyagawa, Shuji
背景：异种移植被认为是解决世界范围内器官短缺的最有吸引力的策略之一。然而，在它将在患者中实现临床使用之前，需要克服许多障碍。一个这样的障碍是有效的免疫抑制策略的发展。我们以前报道过，髓源性抑制细胞（MDSC），一个祖细胞和未成熟髓细胞的异质群体，抑制异种CTL介导的细胞毒性。由于它们的异质性，MDSC可以通过几种抑制机制发挥作用，这些机制破坏先天免疫和适应性免疫。由于巨噬细胞在异种移植排斥反应中起着关键作用，在这项研究中，我们评估了MDSC对巨噬细胞介导的异种排斥反应的抑制作用。（羧基荧光素二乙酸酯，琥珀酰亚胺酯）测定用于评估细胞毒性。虽然，在没有激活的情况下，致敏的MDSC对巨噬细胞诱导的针对SEC细胞的细胞毒性没有可检测的影响，但发现LPS激活的MDSC显著抑制异种细胞毒性。CFSE细胞毒性测定显示MDSC显著抑制巨噬细胞诱导的细胞毒性。此外，吲哚胺2，3双加氧酶（IDO）抑制剂，1-甲基色氨酸（1-MT），取消了MDSC诱导的抑制巨噬细胞介导的异种排斥反应，表明MDSC可能抑制巨噬细胞介导的细胞毒性在IDO依赖marty.Conclusion：这些研究结果表明，MDSC具有很大的潜力，免疫抑制巨噬细胞介导的异种排斥反应。(C)2015 Elsevier B. V.版权所有。
Background: Xenotransplantation is considered to be one of the most attractive strategies for overcoming the worldwide shortage of organs. However, many obstructions need to be overcome before it will achieve clinical use in patients. One such obstacle is the development of an effective immunosuppressive strategy. We previously reported that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of progenitor and immature myeloid cells, suppress xenogenic CTL-mediated cytotoxicity. Because of their heterogeneous nature, MDSC can function via several suppressive mechanisms that disrupt both innate and adaptive immunity. Since macrophages play a pivotal role in the rejection of a xenograft, in this study, we evaluated the suppressive effects of MDSC against macrophage-mediated xenogenic rejection.Materials and methods: To evaluate the effect of monocyte-derived MDSCs on xenogenic immune reactions, a CFSE(carboxyfluorescein diacetate, succinimidyl ester)assay was employed to assess cytotoxicity.Results: While, in the absence of activation, primed MDSCs had no detectable effect on macrophage-induced cytotoxicity against SEC cells, LPS-activated MDSCs were found to significantly suppress xenogenic cytotoxicity. A CFSE cytotoxicity assay revealed that MDSCs significantly suppressed macrophage-induced cytotoxicity. Furthermore, an indoleamine 2,3 dioxygenase (IDO) inhibitor, 1-methyl tryptophan (1-MT), abolished the MDSC-induced suppression of macrophage-mediated xeno-rejection, indicating that MDSCs may suppress macrophage-mediated cytotoxicity in an IDO-dependent manner.Conclusion: These findings indicate that MDSCs have great potential for immunosuppressing macrophagemediated xeno-rejection. (C) 2015 Elsevier B.V. All rights reserved.