Decidual IDO+ macrophage promotes the proliferation and restricts the apoptosis of trophoblasts
Decidual IDO+ macrophage promotes the proliferation and restricts the apoptosis of trophoblasts
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DOI：
10.1016/j.jri.2021.103364
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发表时间：
2021-09-02
影响因子：
3.4
通讯作者：
Li, Da-Jin
中科院分区：
文献类型：
--
作者：
Huang, Hong-Lan;Yang, Hui-Li;Li, Da-Jin
吲哚胺2，3-双加氧酶(IDO)是一种色氨酸分解代谢酶，在生理免疫调节中起重要作用。本研究旨在探讨IDO在早孕蜕膜巨噬细胞(DMPhi)中的表达及其作用。在这里，我们观察到原因不明的复发性自然流产(URSA)患者的IDO+DM Phi显著降低。IDO+DM Phi表现为M2表型，CD206、CD209、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)处理后，DM Phi的M1偏向。对细胞因子阵列和qPCR的进一步分析显示，1-MT处理的DM Phi中滋养层细胞增殖或侵袭相关分子(如CXCL12和BMP2)的水平降低。共培养结果显示，1-MT处理的DMphi抑制HTR-8/Snveo细胞的增殖，降低Ki-67和Bcl2的表达，增加细胞的凋亡率。此外，体外培养的蜕膜基质细胞(DSC)和HTR-8/Snveo细胞以及雌二醇和甲孕酮均可上调U937细胞IDO的表达。这些结果表明，内分泌环境、DSC和滋养层细胞可能是DMphi中IDO水平较高的原因，而具有M2显性表型的IDO DMPhi促进了早孕滋养层细胞的存活。IDO水平的异常降低可能会引发DMphi功能紊乱，进一步抑制滋养细胞的存活，增加流产的风险。
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 (dM phi) during early pregnancy. Here, we observed a remarkable decrease of IDO+ dM phi) from patients with unexplained recurrent spontaneous abortion (URSA). IDO+ dM phi 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 dM phi. 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 dM phi. The data of co-culture system showed that 1-MT-pretreated dM phi 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 dM phi, and IDO dM phi with M2 dominant phenotype promote the survival of trophoblasts during early pregnancy. The abnormal lower level of IDO should trigger the dysfunction of dM phi, further suppress the survival of trophoblasts and increase the risk of miscarriage.