THE MAINTENANCE OF FETAL MATERNAL TOLERANCE IN MARSUPIALS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 免疫学中剩下的一个谜团是，尽管胚胎中的抗原差异是由父亲的等位基因贡献的，但胎儿仍有能力逃避母体免疫系统的排斥。 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“知道”胎儿抗原是外来的。 如何调节母体免疫系统以防止胎儿，特别是胎盘组织的排斥反应尚未完全了解。 一种新的方法来理解胎儿-母体耐受性是如何维持的问题是问“在哺乳动物进化过程中出现了什么机制来适应免疫系统以耐受同种异体胎盘？“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。 在这个提议中，我们使用有袋动物作为哺乳动物生殖进化的替代模型。 本研究中使用了两种有袋动物：南美洲负鼠（Monodelphis astritica），它有一个简单的卵黄囊胎盘;北方棕色袋狸（Isodon macrourus），它有一个绒毛膜尿囊胎盘，与人类和小鼠等真兽目哺乳动物没有什么不同。 这两个物种应该提供有趣的见解如何不同水平的胎盘影响机制的胎儿-母亲的耐受性。 本研究利用NIH资助的M.南极洲

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.