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Decidual Cell/Placental Interactions

蜕膜细胞/胎盘相互作用

基本信息

批准号：
7150651
负责人：
JOAN Sherar HUNT
金额：
$ 28.23万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 2009-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7150651
关键词：
Address Antibodies Antibody Formation Apoptosis Autoimmune Diseases B-Lymphocytes Binding Biological Assay Cells Cellular Immunity Chicago Collaborations Condition Decidual Cell Disease Embryo Enzyme-Linked Immunosorbent Assay Equilibrium Evaluation Family Gene Deletion Gene Expression Genetic Transcription HLA G antigen Human Humoral Immunities Hypoxia Immune system In Situ In Situ Hybridization Inbred NZB Mice Interferons Interleukin-10 Investigation Knock-out Knockout Mice Lead Learning Ligands Maintenance Mediating Membrane Methods Modality Modeling Mothers Mus Natural Killer Cells Necrosis Northern Blotting Numbers Patients Placenta Pre-Eclampsia Pregnancy Pregnant Women Production Protein Overexpression Research Research Personnel Reverse Transcriptase Polymerase Chain Reaction Sampling Serum Testing Transcriptional Regulation Transgenic Organisms Translating Translations Universities Uterus Woman cytokine design improved insight interest mouse model pathogen preference programs promoter receptor research study success trophoblast tumor

项目摘要

DESCRIPTION (provided by applicant): In normal pregnancy the mother's immune system is programmed into a profile where humoral immunity is preferred to cell-mediated immunity. Studies on mechanism(s) underlying the preference for antibody production are very few in number although many investigations have addressed the question of how cell-mediated destruction of the placenta and its membranes might be protected from cytotoxic cells. Recently, we uncovered a likely explantation for high antibody production. When investigating synthesis of non-apoptosis-inducing Tumor Necrosis Family ligands/receptors in human placentas, we learned that BAFF, a promoter of B lymphocyte survival, and APRIL, which binds to the same receptors as BAFF but whose mode of action is not well understood, are transcribed and translated in human placentas. Thus, these two ligands may effect the deviation toward production of antibodies. In this study, we propose three Specific Aims. Aim 1 is to define production of BAFF and APRIL in specific subpopulations of human placental cells and identify conditions controlling transcription and translation. We are particularly interested in two cytokines (IFN 7 and IL-10), hypoxia and soluble HLA-G, and provide some preliminary evidence in support of idea that these molecules, which are associated with early pregnancy and preeclampsia, may be modulators of BAFF and/or APRIL gene expression. In Aim 2 we propose to investigate the effects of gene deletion/overexpression on pregnancy in mice. Our preliminary studies show that both BAFF and APRIL are expressed in mouse placentas, and both transgenic and knockout models are available. Aim 3 is designed to identify relationships between pregnancy and serum levels of BAFF and APRIL in mice, healthy women and women with autioimmune disease. The studies on healthy women prior to and during pregnancy will be assessed in collaboration with C. Ober, University of Chicago. Similar sets of sera from women with autoimmune disorders will be collected by Consultants J. L. Nelson and J. Buyon. The patients will be stratified by disorder and their sera analyzed for levels of BAFF and APRIL. We expect these studies to provide new insights into how pregnancy proceeds without compromising maternal defense against pathogens, to provide important new information on mothers with underlying autoimmune disease, and, ultimately, to lead toward new treatment modalities.

描述（由申请人提供）：在正常妊娠中，母亲的免疫系统被编程为体液免疫优于细胞介导免疫的模式。尽管许多研究已经解决了细胞介导的胎盘及其膜的破坏如何保护免受细胞毒性细胞的影响的问题，但对抗体产生偏好的潜在机制的研究数量很少。最近，我们发现了一种可能的高抗体产生的方法。当研究人胎盘中非凋亡诱导性肿瘤坏死家族配体/受体的合成时，我们了解到BAFF（B淋巴细胞存活的启动子）和APRIL（与BAFF结合相同的受体，但其作用方式尚未完全了解）在人胎盘中转录和翻译。因此，这两种配体可能影响抗体产生的偏差。在这项研究中，我们提出了三个具体目标。目的1是确定在人胎盘细胞的特定亚群中BAFF和APRIL的产生，并确定控制转录和翻译的条件。我们特别感兴趣的两种细胞因子（IFN 7和IL-10），缺氧和可溶性HLA-G，并提供了一些初步证据支持的想法，这些分子，这与早期妊娠和先兆子痫，可能是BAFF和/或APRIL基因表达的调节剂。在目的2中，我们提出研究基因缺失/过表达对小鼠妊娠的影响。我们的初步研究表明，BAFF和APRIL都在小鼠胎盘中表达，并且转基因和敲除模型都是可用的。目的3：探讨小鼠、健康妇女和自身免疫性疾病妇女血清BAFF和APRIL水平与妊娠的关系。将与C.奥伯，芝加哥大学。来自患有自身免疫性疾病的女性的类似血清组将由顾问J. L.纳尔逊和J. Buyon。将按疾病对患者进行分层，并分析其血清的BAFF和APRIL水平。我们希望这些研究能够提供新的见解，了解怀孕如何进行而不影响母体对病原体的防御，为患有潜在自身免疫性疾病的母亲提供重要的新信息，并最终导致新的治疗方式。