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骨髓来源抑制细胞、慢性炎症细胞因子和外泌体 miRNA 的改变导致子宫内膜异位症患者的腹膜免疫紊乱。

Alteration of Myeloid-Derived Suppressor Cells, Chronic Inflammatory Cytokines, and Exosomal miRNA Contribute to the Peritoneal Immune Disorder of Patients With Endometriosis.

机构信息

1 Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.

2 Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, People's Republic of China.

出版信息

Reprod Sci. 2019 Aug;26(8):1130-1138. doi: 10.1177/1933719118808923. Epub 2018 Nov 19.

DOI:10.1177/1933719118808923
PMID:30453861
Abstract

Immunologic disorder has been reported to promote the progression of endometriosis (EMT). It has been known that myeloid-derived suppressor cells (MDSCs) drive the progression of many types of diseases. Few studies have shown the relation between MDSCs and EMT. To test whether MDSCs play a role in the progression of EMT, we defined MDSCs, cytokines, and the exosomal microRNA (miRNA) profile in peritoneal fluid (PF) from EMT patients. Characteristics of MDSCs, regulatory T cells (Tregs) and effector T cells were quantified by flow cytometry. Peritoneal fluid monocyte chemoattractant protein (MCP) 1/3, hepatocyte growth factor (HGF), chemokine (C-X-C motif) ligand (CXCL) 1/2, and 13 other cytokines were performed by enzyme-linked immunosorbent assay kit. Exosomal miRNA sequencing was prepared from PF of 3 women with early-stage EMT, 3 women with advanced stage EMT, and 3 women from control group. Our results showed that accumulations of monocytic MDSCs (Mo-MDSCs) and Tregs were detected in advanced patients with EMT. Patients with EMT displayed a significantly higher production of PF CXCL1, CXCL2, MCP-1, MCP-3, and HGF as compared to those from controls. MicroRNA sequencing showed 13 exosomal miRNAs (miRNA-1908, -130b, -451a, -486-5p, -4488, -432, -342, -425, -505, -6508, -145, -365a, and -365b) which are involved in immune alteration and cell proliferation and were differentially expressed in patients with EMT (fold-change ± 2.0). In conclusion, our study revealed that Mo-MDSCs, inflammatory cytokines, and exosomal miRNA seem to be involved in the progression of EMT; however, the relation between Mo-MDSCs, cytokines, and miRNA needs further research.

摘要

免疫紊乱被报道可促进子宫内膜异位症(EMT)的进展。已知髓源抑制细胞(MDSCs)可促进多种疾病的进展。很少有研究表明 MDSCs 与 EMT 之间存在关系。为了测试 MDSCs 是否在 EMT 的进展中起作用,我们定义了 EMT 患者腹腔液(PF)中的 MDSCs、细胞因子和外泌体 microRNA(miRNA)谱。通过流式细胞术定量了 MDSCs、调节性 T 细胞(Tregs)和效应 T 细胞的特征。通过酶联免疫吸附试验试剂盒检测腹腔液单核细胞趋化蛋白 1/3、肝细胞生长因子(HGF)、趋化因子(C-X-C 基序)配体(CXCL)1/2 和其他 13 种细胞因子。从 3 名早期 EMT 患者、3 名晚期 EMT 患者和 3 名对照组女性的 PF 中制备外泌体 miRNA 测序。我们的结果表明,在晚期 EMT 患者中检测到单核细胞 MDSCs(Mo-MDSCs)和 Tregs 的积聚。与对照组相比,EMT 患者 PF 中 CXCL1、CXCL2、MCP-1、MCP-3 和 HGF 的产生显著增加。miRNA 测序显示 13 种外泌体 miRNA(miRNA-1908、-130b、-451a、-486-5p、-4488、-432、-342、-425、-505、-6508、-145、-365a 和 -365b)参与免疫改变和细胞增殖,并且在 EMT 患者中差异表达(倍数变化±2.0)。总之,我们的研究表明,Mo-MDSCs、炎症细胞因子和外泌体 miRNA 似乎参与 EMT 的进展;然而,Mo-MDSCs、细胞因子和 miRNA 之间的关系需要进一步研究。

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