Trophoblast debris modulates the expression of immune proteins in macrophages: a key to maternal tolerance of the fetal allograft?
Trophoblast debris modulates the expression of immune proteins in macrophages: a key to maternal tolerance of the fetal allograft?
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DOI：
10.1016/j.jri.2012.03.488
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发表时间：
2012-06-01
影响因子：
3.4
通讯作者：
El-Muzaini, M. F.
中科院分区：
文献类型：
--
作者：
Abumaree, M. H.;Chamley, L. W.;El-Muzaini, M. F.
母体免疫细胞和胎盘之间的相互作用是非常重要的，因为妊娠疾病，如反复流产、原因不明的绒毛炎和先兆子痫可能是由于母体免疫系统的适应不足而引起的。在正常妊娠期间，滋养细胞碎片从胎盘大量散落到母体血液中。然后，这些滋养层残留物被迅速从母体循环中清除。在这项研究中，我们将体外胎盘移植模型产生的滋养层碎片暴露于外周血巨噬细胞，并通过ELISA法或流式细胞术对各种在免疫反应中重要的分子进行了定量。滋养细胞碎片的吞噬作用导致巨噬细胞表面MHC-II分子、共刺激分子(CD80、CD86、CD40和B7H3)、单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)和IL-8受体的表达减少，而程序性死亡-1配体1(PD-L1)的表达上调。此外，滋养层残留物的吞噬作用诱导了抗炎细胞因子IL-10、IL-6和IL-1ra的分泌，并减少了促炎细胞因子IL-1β的分泌。巨噬细胞表达IL-12p70和IL-8。滋养层残留物的吞噬作用也增加了巨噬细胞免疫抑制酶吲哚胺2，3-双加氧酶(IDO)的表达。我们已经证明，正常胎盘滋养层残留物的吞噬作用改变了巨噬细胞的表型，从而可能使母亲的免疫反应偏离耐受性，而不是炎症。这可能是允许人类同种异体胎儿移植物在与母体免疫系统直接接触的情况下存活的机制之一。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
Interactions between maternal immune cells and the placenta are of substantial interest since diseases of pregnancy, such as recurrent miscarriage, villitis of unknown etiology and preeclampsia may arise due to inadequate adaptation of the maternal immune system. During normal pregnancy trophoblast debris is shed from the placenta into the maternal blood in large quantities. This trophoblast debris is then rapidly cleared from the maternal circulation. In this study, we exposed trophoblast debris generated from an in vitro placental explant model to peripheral blood-derived macrophages and quantified a variety of molecules that are important in immune responses by ELISA or flow cytometry. Phagocytosis of trophoblast debris resulted in reduced cell-surface expression of MHC-II molecules, the costimulatory molecules (CD80, CD86, CD40 and B7H3), monocyte chemoattractant protein-1 (MCP-1), inter-cellular adhesion molecule 1 (ICAM-1) and IL-8 receptors in macrophages while the expression of programmed death-1 ligand 1 (PD-L1) was upregulated. In addition, phagocytosis of trophoblast debris induced the secretion of the anti-inflammatory cytokines IL-10, IL6 and IL1 Ra and decreased the secretion of pro-inflammatory cytokines IL-1 beta. IL12p70 and IL-8 by macrophages. Phagocytosis of trophoblast debris also increased macrophage expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). We have shown that phagocytosis of trophoblast debris from normal placentae alters the phenotype of macrophages such that they are likely to deviate maternal immune responses towards tolerance and away from inflammation. This may be one of the mechanisms that allow the human fetal allograft to survive in direct contact with the maternal immune system. (c) 2012 Elsevier Ireland Ltd. All rights reserved.