Indoleamine 2, 3-dioxygenase (IDO), a tryptophan-catabolizing enzyme, is essential in physiological immunoregulation. The present research was conducted to elucidate the expression and roles of IDO in decidual macrophages (dMφ) during early pregnancy. Here, we observed a remarkable decrease of IDO⁺ dMφ from patients with unexplained recurrent spontaneous abortion (URSA). IDO⁺ dMφ displayed M2 phenotype with higher CD206, CD209 and CD163, and lower CD86. Interestingly, treatment with 1-methyl-d-tryptophan (1-MT, an IDO pathway inhibitor) led to the M1 bias of dMφ. Further analysis of the cytokine array and the qPCR showed decreased levels of trophoblast proliferation or invasion-related molecules (e.g., CXCL12 and BMP2) in 1-MT-treated dMφ. The data of co-culture system showed that 1-MT-pretreated dMφ decreased the proliferation and the expression of Ki-67 and Bcl-2, and increased cell apoptosis of HTR-8/Snveo cells. Additionally, the expression of IDO in U937 cells was up-regulated by decidual stromal cells (DSC) and HTR-8/Snveo cells in vitro, as well as estradiol and medroxyprogesterone. These data suggest that endocrine environment, DSC and trophoblasts should contribute to the high level of IDO in dMφ, and IDO⁺ dMφ with M2 dominant phenotype promote the survival of trophoblasts during early pregnancy. The abnormal lower level of IDO should trigger the dysfunction of dMφ, further suppress the survival of trophoblasts and increase the risk of miscarriage.

吲哚胺 2, 3-双加氧酶 (IDO) 是一种色氨酸分解代谢酶，在生理免疫调节中是必不可少的。本研究旨在阐明 IDO 在妊娠早期蜕膜巨噬细胞 (dMφ) 中的表达和作用。在这里，我们观察到不明原因复发性自然流产 (URSA) 患者的 IDO ^{+ dMφ 显着降低。}IDO ⁺ dMφ 显示 M2 表型，CD206、CD209 和 CD163 较高，CD86 较低。有趣的是，用 1-甲基-d-色氨酸（1-MT，一种 IDO 途径抑制剂）处理导致 dMφ 的 M1 偏差。对细胞因子阵列和 qPCR 的进一步分析显示滋养层增殖或侵袭相关分子的水平降低（例如, CXCL12 和 BMP2) 在 1-MT 处理的 dMφ 中。共培养系统数据显示，1-MT预处理的dMφ降低了Ki-67和Bcl-2的增殖和表达，增加了HTR-8/Snveo细胞的细胞凋亡。此外，在 U937 细胞中 IDO 的表达在体外被蜕膜基质细胞 (DSC) 和 HTR-8/Snveo 细胞以及雌二醇和甲羟孕酮上调。这些数据表明，内分泌环境、DSC和滋养细胞应有助于dMφ中高水平的IDO，而具有M2显性表型的IDO ⁺ dMφ促进孕早期滋养细胞的存活。IDO异常低水平应引发dMφ功能障碍，进一步抑制滋养细胞存活，增加流产风险。