Immune balance at the foeto-maternal interface as the fulcrum of reproductive success
Immune balance at the foeto-maternal interface as the fulcrum of reproductive success
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DOI：
10.1016/j.jri.2012.10.006
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
Hemberger, Myriam
中科院分区：
文献类型：
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作者：
Hemberger, Myriam
胎生有许多进化上的优势，但随之而来的是半异基因胎儿在怀孕期间必须与母亲共存的问题。在有血液绒毛胎盘的物种中，这个问题尤其明显，因为胎儿滋养层细胞广泛地与母体组织混合，并直接接触母体血液。胎儿和母体的迷人适应使这种相互作用从免疫排斥反应转向免疫耐受，实际上也转向积极支持生殖成功。最近的数据表明，其中一些显著的适应在老鼠和人类之间是保守的。因此，直接暴露在母体子宫环境中的一组滋养层细胞具有在其表面表达一种不寻常的抗原库的特征。父系抗原可以被母体免疫细胞，特别是表达同源受体的子宫自然杀伤细胞识别，以调节植入部位发生的广泛的重塑事件。在小鼠身上进行的详细的基因解剖实验进一步证明了抗原差异对胎儿生长的直接影响。随着近交系的出现，滋养层干细胞的体外培养系统，以及深入的遗传、基因组和表观基因组数据，小鼠将成为研究胎儿-母体边界复杂的免疫串扰的有价值的模型系统。这些见解将为揭示滋养细胞与其周围母体环境之间的相互和协同作用铺平道路，从而有助于理解怀孕病理。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
Viviparity has many evolutionary advantages but brings with it the problem of the semi-allogeneic foetus having to coexist with the mother for the duration of pregnancy. In species with haemochorial placentation this problem is particularly evident as foetal trophoblast cells are extensively intermingled with maternal tissue and are directly exposed to maternal blood. Fascinating adaptations on both the foetal and maternal side have allowed for this interaction to be re-directed away from an immune rejection response not only towards immunotolerance, but in fact towards actively supporting reproductive success. Recent data have shown that some of these remarkable adaptations are conserved between mice and humans. Thus, a subset of trophoblast cells that is directly exposed to the maternal uterine environment shares the feature of expressing an unusual antigen repertoire on their surface. Paternal antigens can be recognized by maternal immune cells, in particular uterine natural killer cells that express cognate receptors, to regulate the extensive remodelling events that take place at the implantation site. Detailed genetic dissection experiments in the mouse have further demonstrated the direct impact of antigenic dissimilarity on foetal growth. With the availability of inbred strains, in vitro culture systems of trophoblast stem cells, and in-depth genetic, genomic and epigenomic data the mouse will be a valuable model system to study the intricate immune crosstalk at the foeto-maternal boundary. These insights will pave the way towards unravelling the mutual and synergistic interactions between trophoblast and its surrounding maternal environment, and in doing so help understand pregnancy pathologies. (C) 2012 Elsevier Ireland Ltd. All rights reserved.