An elevated level of IL-10 has been considered a critical factor for the development of endometriosis; however, its detailed mechanism and causal relationship remain unclear. This study explored the cellular source and angiogenic activity of local IL-10 during the early stage of endometriosis. Using a surgical murine model, we found that localised treatment with exogenous recombinant IL-10 on the day of surgery significantly enhanced endometriotic lesion growth and angiogenesis, whereas blocking local IL-10 activity using mAbs significantly suppressed those effects. Adoptive transfer of Il10+/+ plasmacytoid dendritic cells into mice significantly enhanced lesion development, whereas Il10-/- plasmacytoid dendritic cells significantly inhibited lesion development. Furthermore, in vitro angiogenesis analyses demonstrated that the IL-10 and IL-10 receptor pathway stimulated the migratory and tube formation ability of HUVECs as well as ectopic endometrial mesenchymal stem cells through, at least in part, a VEGF-dependent pathway. We also found that recombinant IL-10 directly stimulated angiogenesis, based on a Matrigel plug assay as well as a zebrafish model. Pathological results from human endometrioma tissues showed the increased infiltration of CD123+ plasmacytoid dendritic cells and higher percentages of cells that express the IL-10 receptor and CD31 as compared with the corresponding normal counterparts. Taken together, these results show that IL-10 secreted from local plasmacytoid dendritic cells promotes endometriosis development through pathological angiogenesis during the early disease stage. This study provides a scientific basis for a potential therapeutic strategy targeting the IL-10-IL-10 receptor pathway in the endometriotic milieu. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

中文翻译：

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来自浆细胞样树突状细胞的IL-10在子宫内膜异位症的早期促进血管生成。

IL-10水平升高被认为是子宫内膜异位症发展的关键因素。但是，其详细机制和因果关系仍不清楚。这项研究探讨了子宫内膜异位症早期局部IL-10的细胞来源和血管生成活性。使用手术鼠模型，我们发现在手术当天用外源重组IL-10进行局部治疗可显着增强子宫内膜异位病灶的生长和血管生成，而使用mAb阻断局部IL-10活性则可显着抑制这些作用。Il10 + / +浆细胞样树突状细胞向小鼠的过继转移显着增强了病变的发展，而Il10-/-浆细胞样树突状细胞显着抑制了病变的发展。此外，体外血管生成分析表明，IL-10和IL-10受体途径至少部分通过VEGF依赖性途径刺激了HUVEC以及异位子宫内膜间充质干细胞的迁移和管形成能力。我们还发现，基于Matrigel塞测定法和斑马鱼模型，重组IL-10可直接刺激血管生成。来自人类子宫内膜瘤组织的病理结果表明，与相应的正常对应物相比，CD123 +浆细胞样树突状细胞的浸润增加，表达IL-10受体和CD31的细胞百分比更高。综上所述，这些结果表明，从局部浆细胞样树突状细胞分泌的IL-10在疾病早期通过病理性血管生成促进子宫内膜异位症的发展。这项研究为针对子宫内膜异位症环境中的IL-10-IL-10受体途径的潜在治疗策略提供了科学依据。©2019作者。John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版的《病理学杂志》。