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超越免疫抑制作用:髓系来源的抑制性细胞在骨相关疾病中的双重作用。

Beyond immunosuppressive effects: dual roles of myeloid-derived suppressor cells in bone-related diseases.

机构信息

Department of Orthopaedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

Department of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, 400038, China.

出版信息

Cell Mol Life Sci. 2021 Dec;78(23):7161-7183. doi: 10.1007/s00018-021-03966-9. Epub 2021 Oct 11.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells (IMCs) with immunosuppressive functions, whereas IMCs originally differentiate into granulocytes, macrophages, and dendritic cells (DCs) to participate in innate immunity under steady-state conditions. At present, difficulties remain in identifying MDSCs due to lacking of specific biomarkers. To make identification of MDSCs accurately, it also needs to be determined whether having immunosuppressive functions. MDSCs play crucial roles in anti-tumor, angiogenesis, and metastasis. Meanwhile, MDSCs could make close interaction with osteoclasts, osteoblasts, chondrocytes, and other stromal cells within microenvironment of bone and joint, and thereby contributing to poor prognosis of bone-related diseases such as cancer-related bone metastasis, osteosarcoma (OS), rheumatoid arthritis (RA), osteoarthritis (OA), and orthopedic trauma. In addition, MDSCs have been shown to participate in the procedure of bone repair. In this review, we have summarized the function of MDSCs in cancer-related bone metastasis, the interaction with stromal cells within the bone microenvironment as well as joint microenvironment, and the critical role of MDSCs in bone repair. Besides, the promising value of MDSCs in the treatment for bone-related diseases is also well discussed.

摘要

髓系来源抑制细胞(MDSCs)是一群具有免疫抑制功能的不成熟髓系细胞(IMCs),而 IMCs 最初在稳态条件下分化为粒细胞、巨噬细胞和树突状细胞(DCs),参与固有免疫。目前,由于缺乏特异性生物标志物,MDSCs 的鉴定仍然存在困难。为了准确鉴定 MDSCs,还需要确定其是否具有免疫抑制功能。MDSCs 在抗肿瘤、血管生成和转移中发挥着关键作用。同时,MDSCs 可以与骨和关节微环境中的破骨细胞、成骨细胞、软骨细胞和其他基质细胞密切相互作用,从而导致与骨相关的疾病(如癌症骨转移、骨肉瘤(OS)、类风湿关节炎(RA)、骨关节炎(OA)和骨科创伤)预后不良。此外,已经表明 MDSCs 参与骨修复过程。在这篇综述中,我们总结了 MDSCs 在癌症骨转移中的作用、与骨微环境和关节微环境中基质细胞的相互作用,以及 MDSCs 在骨修复中的关键作用。此外,还讨论了 MDSCs 在治疗与骨相关疾病方面的潜在价值。

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