Indoleamine 2, 3-dioxygenase (IDO) catabolizes tryptophan, mediates immunomodulatory functions, and is released by stromal cells such as mesenchymal stem cells. The aims of this study were to investigate the effects of IDO silencing on immunosuppressive function of adipose-derived mesenchymal stem cells (ASCs), T cells phenotype, and the proliferation/migration of tumor cells. ASCs isolated from adipose tissues of healthy women were transfected with IDO-siRNA. Galectin-3, transforming growth factor-β1, hepatocyte growth factor, and interleukin-10 as immunomodulators were measured in ASCs using qRT-PCR. T cells phenotype, interferon-γ, and interleukin-17 expression were evaluated in peripheral blood lymphocytes (PBLs) cocultured with IDO silenced-ASCs by flow cytometry and qRT-PCR, respectively. Scratch assay was applied to assess the proliferation/migration of MDA-MB-231 cell line. Galectin-3 was upregulated (p ˂ 0.05) while hepatocyte growth factor was downregulated (p ˂ 0.05) in IDO-silenced ASCs compared to control groups. Regulatory T cells were inhibited in PBLs cocultured with IDO-silenced ASCs; also T helper2 was decreased in PBLs cocultured with IDO-silenced ASCs relative to the scramble group. IDO-silenced ASCs caused interferon-γ overexpression but interleukin-17 downregulation in PBLs. The proliferation/migration of MDA-MB-231 was suppressed after exposing to condition media of IDO-silenced ASCs compared with condition media of untransfected (p < 0.01) and scramble-transfected ASCs (p < 0.05). The results exhibited the weakened capacity of IDO-silenced ASCs for suppressing the immune cells and promoting the tumor cells' proliferation/migration. IDO suppression may be utilized as a strategy for cancer treatment. Simultaneous blocking of immunomodulators along with IDO inhibitors may show more effects on boosting the efficiency of immune-based cancer therapies.

中文翻译：

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吲哚胺 2, 3-双加氧酶 (IDO) 沉默对脂肪间充质干细胞 (ASCs) 免疫调节功能和促癌特性的影响

吲哚胺 2, 3-双加氧酶 (IDO) 分解色氨酸，介导免疫调节功能，并由间充质干细胞等基质细胞释放。本研究的目的是研究 IDO 沉默对脂肪间充质干细胞 (ASCs) 的免疫抑制功能、T 细胞表型和肿瘤细胞增殖/迁移的影响。用 IDO-siRNA 转染从健康女性脂肪组织中分离的 ASC。使用 qRT-PCR 在 ASC 中测量作为免疫调节剂的半乳糖凝集素 3、转化生长因子-β1、肝细胞生长因子和白细胞介素 10。分别通过流式细胞术和 qRT-PCR 在与 IDO 沉默的 ASC 共培养的外周血淋巴细胞 (PBL) 中评估 T 细胞表型、干扰素-γ 和白细胞介素 17 的表达。划痕法用于评估 MDA-MB-231 细胞系的增殖/迁移。Galectin-3 上调（p˂  0.05)，而 与对照组相比，IDO 沉默的 ASC 中肝细胞生长因子下调 ( p˂ 0.05)。在与 IDO 沉默的 ASC 共培养的 PBL 中，调节性 T 细胞受到抑制；相对于加扰组，在与 IDO 沉默的 ASC 共培养的 PBL 中，T helper2 也减少了。IDO 沉默的 ASC 导致干扰素-γ 过表达，但白细胞介素 17 在 PBL 中下调。与未转染 ( p  < 0.01) 和乱序转染的 ASC ( p < 0.05)。结果表明IDO沉默的ASCs抑制免疫细胞和促进肿瘤细胞增殖/迁移的能力减弱。IDO 抑制可用作癌症治疗的策略。同时阻断免疫调节剂和 IDO 抑制剂可能会对提高基于免疫的癌症治疗的效率产生更多影响。