THE MAINTENANCE OF FETAL MATERNAL TOLERANCE IN MARSUPIALS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。尽管胚胎中的抗原差异是由父亲的等位基因造成的，但胎儿逃避母体免疫系统排斥的能力仍是免疫学中尚存的谜团之一。从胎盘哺乳动物，特别是人类的研究中可以清楚地看出，母体免疫系统“意识到”胎儿抗原是外来的。母体免疫系统是如何被调节以防止胎儿，特别是胎盘组织的排斥反应的，目前还不完全清楚。一种理解胎儿-母体耐受是如何维持的新方法是问，“哺乳动物进化过程中出现了什么机制来适应免疫系统来耐受异体胎盘？”这个问题只能通过对哺乳动物胎儿-母体相互作用的比较分析来回答。在这个建议中，我们使用有袋动物作为哺乳动物繁殖进化的替代模型。本研究使用了两种有袋动物；南美负鼠（Monodelphis domestica）有一个简单的卵黄囊胎盘，北方棕色土鼬（Isoodon macrourus）有一个绒毛膜-尿囊胎盘，与人类和老鼠等真动物哺乳动物没有什么不同。这两个物种应该为不同水平的胎盘如何影响胎儿-母体耐受机制提供有趣的见解。这项研究利用了美国国立卫生研究院资助的家蝇全基因组序列。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One of the remaining enigmas in immunology is the ability of the fetus to escape rejection by the maternal immune system despite antigenic differences in the embryo contributed by paternal alleles. It is clear from studies in placental mammals, humans in particular, that the maternal immune system is "aware" of the fetal antigens as foreign. How the maternal immune system is regulated to prevent rejection of fetal, specifically placental tissues, is not completely understood. A novel approach to understanding the problem of how fetal-maternal tolerance is maintained is to ask, "what mechanisms appeared during mammalian evolution to adapt the immune system to tolerate an allogeneic placenta?" This question can only be answered through comparative analysis of mammalian fetal-maternal interactions. In this proposal we are using marsupials as the alternative models of evolution of mammalian reproduction. Two species of marsupials are used in this study; the South American opossum, Monodelphis domestica, which has a simple yolk sac placenta and the Northern brown bandicoot, Isoodon macrourus, which has a chorio-allantoic placenta, not unlike eutherian mammals such as humans and mice. These two species should provide interesting insights into how different levels of placentation affect mechanisms of fetal-maternal tolerance. This study takes advantage of the NIH funded whole genome sequence of M. domestica.