Immunomodulation by Pregnancy Specific Glycoprotein 17

妊娠特异性糖蛋白 17 的免疫调节

基本信息

批准号：
7151232
负责人：
Gabriela S Dveksler
金额：
$ 31.72万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-12-15 至 2008-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7151232
关键词：
Affect Alloantigen Anti-Inflammatory Agents Anti-inflammatory Antibodies Antigen-Presenting Cells Apoptosis Area Autoimmune Diseases Bacterial Antigens Binding Biological Biological Process Blood Circulation CD4 Positive T Lymphocytes Cell Differentiation process Cell Maturation Cell Proliferation Cell Survival Cell surface Cells Collaborations Compatible Complex Dendritic Cells Development Disease Environment Family Fathers Fc Receptor Generations Genes Giant Cells Glycoproteins Goals Helper-Inducer T-Lymphocyte Hormones Human Humoral Immunities Immune Immune response Immune system Immunity In Vitro Inherited Investigation Knowledge Ligands Mediating Mediator of activation protein Mesentery Monkeys Mothers Mus Nature Nematoda Numbers Outcome Parasites Pathology Patient currently pregnant Peripheral Placenta Play Pregnancy Pregnancy loss Pregnant Women Preparation Primates Process Protein Family Purpose Reagent Recurrence Regulation Reporting Research Rodent Role Serum Signal Transduction Spontaneous abortion Syncytiotrophoblast T-Lymphocyte Techniques Th2 Cells Time Transgenic Mice Transmembrane Domain Transplantation Trichuris Woman Work base cytokine defined contribution extracellular fetal human PHEMX protein immunoregulation implantation in vivo lymph nodes macrophage member novel therapeutics pathogen programs receptor research study response success

项目摘要

The mechanisms responsible for the protection of the fetal semiallograft from attack by the matemal immune system are complex and remain incompletely understood. Establishemnt of a type-2 (TH2) immune response is believed to be one 'of the key factors responsible for pregnancy success as well as for the decreases in disease activity in pregnant women suffering from certain autoimmune diseases. Hormones and eytokines produced by the placenta have been implicated in the generation of the TH2 environment. Pregnancy specific glycoproteins (PSGs) are produced by the placenta and are secreted into the maternal circulation from the time of implantation. Neutralization of PSGs by Abs leads to spontaneous abortion and PSGs induce the secretion of anti-inflammatory cytokines.These findings suggest that PSGs may have an important role in regulation of the immune response during pregnancy. Our long-term goal is to define the roles and mechanisms of action of PSGs in normal and abnormal pregnancies. The central hypothesis of this application is that murine PSG 17 contributes to the establishment of an immune environment favoring a TH2 immune response. The rationale behind the proposed research is that a better understanding of the role of PSGs in controlling immunity during pregnancy could result in the implementation of new therapies for women suffering of recurrent pregnancy losses and other immune-based pathologies. To accomplish the objectives of this applieationwe will pursue three specific aims: (1) Determine whether PSG17-CD9 interactions provide a co-stimulatory signal that stimulates naive CD4 T cell differentiation to CD4 effector T helper cells. This will be accomplished by establishing whether binding of PSG17 to its receptor CD9 affects the proliferation of these cells and the cytokines they secrete. (2) Determine whether PSG17 binding to APC favors TH2 cell development before and after Ag encounter. For this purpose, we will evaluate the effects of P SG 17 treatment of dendritic cells and the effects of P SG 17 treatment in APC in their ability to induce differentiation of T cells derived from TcR transgenic mice upon primary and secondary stimulaton. (3) Determine the nature of the in vivo response of non-pregnant PSG17-expressing mice to a parasite. Mice injected with PSG17 will be challenged with Trichuris muris and the cytokine expression in mesenteric lymph nodes, total serum Ig levels and worm burden will be analyzed.

负责保护胎儿半斜移植的机制是由Matemal Immune系统发作的复杂并保持不完全理解。建立2型2（th2）免疫反应被认为是一种 '导致妊娠成功以及孕妇疾病活动减少的关键因素患有某些自身免疫性疾病。胎盘产生的激素和Eytokines已与 TH2环境的产生。特定于妊娠的糖蛋白（PSG）是由胎盘产生的，是从植入时间开始分泌到孕产妇的循环中。通过ABS中和PSG导致自发流产和PSG诱导抗炎细胞因子的分泌。这些发现表明PSGS 在怀孕期间的免疫反应调节中可能具有重要作用。我们的长期目标是定义 PSG在正常和异常妊娠中的作用和作用机理。中心假设应用是鼠PSG 17有助于建立有利于Th2免疫的免疫环境回复。拟议的研究背后的理由是，更好地了解PSG在控制中的作用怀孕期间的免疫力可能导致针对经常出现的妇女实施新的疗法怀孕损失和其他基于免疫的病理。为了实现此应用的目标，我们将追求三个特定目的：（1）确定PSG17-CD9相互作用是否提供了刺激的共刺激信号幼稚的CD4 T细胞与CD4效应T辅助细胞的分化。这将通过确定是否是否 PSG17与其受体CD9的结合会影响这些细胞的增殖和它们分泌的细胞因子。（2）确定PSG17与APC的结合是否有利于Ag相遇之前和之后的Th2细胞发育。为了这目的，我们将评估P SG 17的树突状细胞治疗的影响以及P SG 17在APC中的影响它们能够诱导从TCR转基因小鼠衍生的T细胞分化在原发性和次级上刺激。（3）确定非妊娠PSG17小鼠对寄生虫的体内反应的性质。老鼠注射PSG17将被trichuris muris和肠系膜淋巴结中的细胞因子表达挑战，将分析总血清Ig水平和蠕虫负担。