CD1d is a novel cell-surface marker for human monocytic myeloid-derived suppressor cells with T cell suppression activity in peripheral blood after allogeneic hematopoietic stem cell transplantation

CD1d is a novel cell-surface marker for human monocytic myeloid-derived suppressor cells with T cell suppression activity in peripheral blood after allogeneic hematopoietic stem cell transplantation
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DOI:
10.1016/j.bbrc.2017.11.010
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发表时间:
2018-01-01
影响因子:
3.1
通讯作者:
Hong, Seok-Ho
Hong, Seok-Ho
中科院分区:
生物学4区
文献类型:
--
作者:
An, Borim;Lim, Ji-Young;Hong, Seok-Ho

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髓源性抑制细胞(MDSCs)是一种异质细胞群,在癌症和各种病理条件下调节免疫反应。然而,人类MDSCs的表型和功能异质性是开发靶向或调节MDSCs治疗肿瘤进展、炎症和移植物抗宿主病(GVHD)治疗策略的主要障碍。我们之前的研究表明,循环HLA-DR(-)CD14(+)单核细胞MDSCs是异基因造血干细胞移植(alloo - hsct)后临床结果的主要贡献者。在这项研究中,我们通过高通量筛选,发现了一组在接受同种异体造血干细胞移植患者外周血(PB)中分离的HLA-DR-CD14+单核细胞MDSCs中强烈表达的表面标记物。随后的实验表明,与粒细胞MDSCs相比,CD1d在同种异体造血干细胞PB的单核细胞MDSCs中具有一致的优势表达。此外,与CD1d(-)细胞相比,从同种异体造血干细胞患者的PB中分离的表达CD1d的细胞具有抑制T细胞增殖的活性,MyD88和IDO的表达更高。我们的研究结果表明,CD1d可能是一个有价值的标志物,用于进一步评估人类单核细胞MDSCs治疗免疫相关疾病,包括GVHD。(C) 2017爱思唯尔公司版权所有。
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that regulate immune responses in cancer and various pathological conditions. However, the phenotypic and functional heterogeneity of human MDSCs represents a major hurdle for the development of therapeutic strategies targeting or regulating MDSCs in tumor progression, inflammation, and graft-versus-host disease (GVHD). We previously shown that circulating HLA-DR(-)CD14(+) monocytic MDSCs are a major contributor to clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we identified, using high-throughput screening, a set of surface markers that are strongly expressed in HLA-DR-CD14+ monocytic MDSCs isolated from the peripheral blood (PB) of patients receiving allo-HSCT. Subsequent experiments showed the consistent dominant expression of CD1d in monocytic MDSCs of allo-HSCT PB in comparison with granulocytic MDSCs. In addition, CD1d-expressing cells isolated from PB of allo-HSCT patients showed the suppressive activity of T cell proliferation and higher expression of MyD88 and IDO compared with CD1d(-) cells. Our results suggest that CD1d could be a valuable marker for further therapeutic evaluation of human monocytic MDSCs for immune-related diseases, including GVHD. (C) 2017 Elsevier Inc. All rights reserved.