Glycodelin A Induces a Tolerogenic Phenotype in Monocyte-Derived Dendritic Cells In vitro
Glycodelin A Induces a Tolerogenic Phenotype in Monocyte-Derived Dendritic Cells In vitro
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DOI：
10.1111/j.1600-0897.2008.00647.x
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发表时间：
2008-12-01
影响因子：
3.6
通讯作者：
Jeschke, Udo
中科院分区：
文献类型：
--
作者：
Scholz, Christoph;Toth, Bettina;Jeschke, Udo
成功的哺乳动物怀孕需要在母胎界面上保持微妙的免疫平衡，使半异基因胎儿能够成长，同时保护母亲和孩子免受环境病原体的影响。与其他粘膜组织一样，树突状细胞(DC)等专业抗原提呈细胞对抗原的识别和处理决定了后续免疫反应的进程。胎儿-母体交界处的DC有助于形成这种免疫平衡。子宫内膜组织在可育窗期(即胚泡着床时间)分泌大量糖蛋白A(GDA)。我们研究了GDA对单核细胞来源的DC(MoDC)表面标志物表达、胞内吞噬活性、细胞因子谱以及淋巴组织增殖活性的影响。经GDA预处理后，经肿瘤坏死因子-α和白介素1-β成熟后，moDC的共刺激分子表达减少，主要组织相容性复合体-II表达不变，DC-SIGN阳性细胞持续存在。经GDA处理的MODC具有更高的内吞噬细胞活性，增加了IL-10的产生，并呈剂量依赖性地降低淋巴增殖活性。GDA单独孵育并没有改变未成熟的表型。我们的结果表明，在这个模型中，人类子宫内膜在着床期间分泌大量的GDA，从而有助于通过蜕膜树突状细胞形成母亲和胎儿之间独特的免疫相互作用。
Successful mammalian pregnancy requires a delicate immunological balance at the feto-maternal interface that allows the semi-allogeneic fetus to grow, while protecting mother and child from environmental pathogens. As in other mucosal tissues, antigen-recognition and -handling by professional antigen-presenting cells such as dendritic cells (DC) determine the course of the subsequent immune response. DC at the feto-maternal interface help shape this immunological equilibrium. Endometrial tissue secretes high quantities of glycodelin A (GdA) during the so-called fertile window (i.e. the time of implantation of the blastocyst).We investigated the effect of GdA on monocyte-derived DC (moDC) regarding surface marker expression, endopinocytotic activity, cytokine profile as well as lymphoproliferative activity.Upon pretreatment with GdA and subsequent maturation with tumor necrosis factor-alpha and interleukin (IL)-1 beta, moDC displayed a reduced expression of costimulatory molecules, an unchanged major histocompatibility complex-II expression and persistence of DC-SIGN positive cells. GdA-pretreated moDC had a higher endopinocytotic activity, an increased IL-10 production and a dose-dependent reduction in lymphoproliferative activity. GdA incubation alone did not alter the immature phenotype.Our results suggest a model in which the human endometrium secretes high quantities of GdA during implantation and thereby helps to shape the unique immunological interaction between mother and fetus via decidual DC.