Objectives

This study aimed to determine the systemic and local proportions, focal localization, and characteristics of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in endometriosis.

Study design

Peripheral blood and peritoneal fluid were obtained from patients with a benign gynecologic condition (controls) or endometriosis. PMN-MDSCs were defined as CD33⁺HLA-DR^low/−CD14⁻CD15⁺ and monocytic (M)-MDSCs were defined as CD33⁺HLA-DR^low/−CD14⁺CD15⁻, and were identified using flowcytometry. Ovarian endometriotic tissues were obtained, and the expression of lectin-type oxidized low density lipoprotein receptor-1 (LOX1) as a marker of PMN-MDSCs, arginine 1 (Arg1), and matrix metalloproteinase 9 (MMP9) were detected using immunohistochemistry. Anti-Ly6G antibody was administered to endometriosis model mice, and the number and weight of the lesions were measured, and cell proliferations and apoptosis in the lesions were analyzed using Ki67 immunohistochemistry and TUNEL assay.

Results

In the peripheral blood, the proportion of PMN-MDSCs was significantly higher in endometriosis (3.20 vs 1.63 %, p < 0.05), but the proportion of M-MDSCs did not differ between the groups. In the peritoneal fluid, the proportion of PMN-MDSCs was significantly higher in endometriosis (7.82 × 10⁻¹% vs 6.48 × 10^-2%, p < 0.05), whereas the proportion of M-MDSCs did not differ between the groups. PMN-MDSCs were detected in the stromal cell layer of the endometriotic cyst wall. Double staining for LOX1 and Arg1, and LOX1 and MMP9 was confirmed. Administration of Ly6G antibody did not change the number or weight of endometriosis lesions, but significantly decreased Ki67-positive cells and increased TUNEL-positive cells in the lesions.

Conclusions

PMN-MDSCs may contribute to the pathogenesis of endometriosis via Arg1 and MMP9 expression.

中文翻译：

---

多形核髓源性抑制细胞在子宫内膜异位症中的作用

目标

本研究旨在确定子宫内膜异位症中多形核髓源性抑制细胞 (PMN-MDSCs) 的全身和局部比例、病灶定位和特征。

学习规划

从患有良性妇科疾病（对照）或子宫内膜异位症的患者中获取外周血和腹膜液。PMN-MDSC 被定义为 CD33 ⁺ HLA-DR^低/- CD14 ^- CD15 ⁺和单核细胞 (M)-MDSC 被定义为 CD33 ⁺ HLA-DR^低/- CD14 ⁺ CD15 ^-, 并使用流式细胞仪进行鉴定。获得卵巢子宫内膜异位组织，免疫组化检测作为PMN-MDSCs标志物的凝集素型氧化低密度脂蛋白受体1（LOX1）、精氨酸1（Arg1）和基质金属蛋白酶9（MMP9）的表达。给予子宫内膜异位症模型小鼠抗Ly6G抗体，测量病灶数量和重量，采用Ki67免疫组化和TUNEL法分析病灶内细胞增殖和凋亡情况。

结果

在外周血中，子宫内膜异位症中 PMN-MDSCs 的比例显着升高（3.20 vs 1.63 %，p < 0.05），但 M-MDSCs 的比例在各组之间没有差异。在腹膜液中，PMN-MDSCs 的比例在子宫内膜异位症中显着更高（7.82 × 10 ^-1 % vs 6.48 × 10 ^-2 %，p < 0.05），而 M-MDSCs 的比例在各组之间没有差异。在子宫内膜异位囊肿壁的基质细胞层中检测到 PMN-MDSCs。确认了 LOX1 和 Arg1 以及 LOX1 和 MMP9 的双重染色。Ly6G抗体的施用并未改变子宫内膜异位症病灶的数量或重量，但显着减少了病灶中的Ki67阳性细胞和增加了TUNEL阳性细胞。

结论

PMN-MDSCs 可能通过 Arg1 和 MMP9 的表达参与子宫内膜异位症的发病机制。