mdsc来源的树突状细胞的分化和免疫功能。

IF 1.2 Q4 GENETICS & HEREDITY Global Medical Genetics Pub Date : 2022-12-01 DOI:10.1055/s-0042-1756659
Zequn Ding, Yan Zhang
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引用次数: 0

摘要

树突状细胞(dc)在启动和调节免疫反应中起着关键作用,除了它们在体内的作用外,树突状细胞还被用作各种肿瘤疫苗的天然佐剂。在体外,单核细胞可用于诱导DCs,但在肿瘤患者中,由于骨髓造血功能不足,髓外造血和肿瘤相关髓样细胞扩增,单核细胞主要以髓源性抑制细胞(myeloid-derived suppressor cells, MDSCs)的形式存在。本实验旨在探讨MDSCs在肿瘤患者诱导的dc分化及免疫功能的差异。在小鼠模型中,我们使用正常小鼠骨髓细胞衍生的dc作为对照细胞,在荷瘤模型中,我们诱导脾脏中的MDSCs生成dc (MDSC-DCs)。通过流式细胞术,我们发现MDSC-DCs的产量明显高于对照小鼠,并且MDSC-DCs的干扰素-γ分泌明显减少。通过OVA抗原呈递实验,我们发现MDSC-DCs的抗原呈递能力明显降低。通过对荷瘤小鼠细胞的过继处理,我们发现MDSC-DCs的抗肿瘤免疫功能明显降低。随后,我们探讨了MDSC-DCs免疫功能活性降低的机制。我们通过流式细胞术检测MDSC-DCs的表面标记物发生了变化。通过流式分选和RNA测序,我们发现MDSC-DCs中的一些通路和关键基因表达发生了变化。综上所述,本研究发现MDSC-DCs的免疫功能下降,并探讨了免疫功能活性下降的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Differentiation and Immunological Function of MDSC-Derived Dendritic Cells.

Dendritic cells (DCs) play a key role in initiating and regulating immune responses, and in addition to their roles in vivo, DCs are used as natural adjuvants for various tumor vaccines. In vitro, monocytes can be used to induce DCs, but in tumor patients, due to insufficient bone marrow hematopoiesis, extramedullary hematopoiesis and tumor-associated myeloid cells expand, and monocytes mainly exist in the form of myeloid-derived suppressor cells (MDSCs). The purpose of this experiment was to explore the differences in the differentiation and immune function of DCs induced by MDSCs in tumor patients. In a mouse model, we used normal mouse bone marrow cell-derived DCs as control cells, and in a tumor-bearing model, we induced MDSCs in the spleen to generate DCs (MDSC-DCs). Through flow cytometry, we found that the production of MDSC-DCs was significantly higher than that of control mice, and the secretion of interferon-γ of MDSC-DCs was significantly reduced. Through OVA antigen presentation experiments, we found that the antigen presentation ability of MDSC-DCs was significantly decreased. Through adoptive treatment of tumor-bearing mice cells, we found that the antitumor immune function of MDSC-DCs was significantly reduced. After that, we explored the mechanism of the decrease of immune function activity of MDSC-DCs. We determined that the surface markers of MDSC-DCs were changed by flow cytometry. Through flow sorting and RNA sequencing, we found that some pathways and key gene expression in MDSC-DCs were changed. In conclusion, this study found that the immune function of MDSC-DCs decreased and explored the mechanism of the decreased immune function activity.

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来源期刊
Global Medical Genetics
Global Medical Genetics GENETICS & HEREDITY-
自引率
11.80%
发文量
30
审稿时长
14 weeks
期刊最新文献
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