KFO 296: Feto-maternal immune cross talk:Consequences for maternal and offspring's health

在过去的几十年里，人们对母体免疫和内分泌对妊娠的适应有了更好的了解。这种适应创造了一个耐受性生态位，在这个生态位中，这些半同种异体的胎儿可以成功地发育到足月。同时，这种适应对产妇健康有利，也有不利之处。它可以改善母体自身免疫性疾病的活动性，如多发性硬化症（MS），但增加感染的严重程度，如流感。此外，孕妇在怀孕期间对适应能力的挑战，如免疫力低下和患慢性免疫疾病的风险增加，可能会对儿童今后的健康造成不利影响。产前挑战包括产前压力感知和药物治疗。今天，跨学科的途径开发参与调解这些临床相关的优势和劣势，为孕产妇和儿童的健康仍然很大程度上被忽视。这种忽视是由于医学领域之间的交流普遍有限。在这个合作项目中，我们通过联合来自不同医学学科的临床医生和基础科学家来克服这一限制。作为汉堡大学医学院（UKE）和Heinrich-Pette-Institute（莱布尼茨实验病毒学研究所）的一个严格的跨学科临床研究单位，我们现在寻求共同解决两个关键目标。首先，我们的目的是确定产妇对妊娠的适应如何对MS患者或流感感染期间的产妇健康产生有利或不利的后果。其次，我们的目标是确定在产前压力或对乙酰氨基酚或类固醇药物的影响下，母体对妊娠的适应受到挑战是如何对胎儿免疫发育和后代的出生后免疫不利的。这些目标的概念如图1所示。我们已经建立了相应的小鼠模型，反映了人类各自的免疫疾病。我们还可以接触到孕妇，最终是她们的孩子，以便将小鼠模型的发现转化为临床应用，反之亦然。现在，这为我们实现目标提供了一个平台。预期的见解将为生物蛋白发现奠定基础，并为改善人类不良免疫反应的干预提供机会。

An improved understanding of the maternal immune and endocrine adaptation to pregnancy hasemerged over the last decades. This adaptation creates a tolerogenic niche, in which thesemiallogenic fetus can successfully develop until term. Concomitantly, this adaptation bearsadvantages, and also disadvantages for maternal health. It may improve maternal autoimmunedisease activity, as seen in Multiple sclerosis (MS), but enhances severity of infections, such asinfluenza. Also, disadvantages for children¿s health later in life can arise from challenges to thematernal adaptation during pregnancy, such as a poor immunity and an increased risk for chronicimmune diseases. Prenatal challenges include prenatal stress perception and medication. Todate, the interdisciplinary exploitation of pathways involved in mediating these clinically relevantadvantages and disadvantages for maternal and children¿s health is still largely neglected. Thisneglect is attributed to a generally limited exchange between medical fields. In this collaborativeprogram, we have overcome this limitation by allying clinicians and basic scientists from differentmedical disciplines.Structured as a rigorously interdisciplinary clinical research unit based at the Medical Faculty ofthe University of Hamburg (UKE) and the Heinrich-Pette-Institute, a Leibniz Institute forExperimental Virology, we now seek to jointly address two key aims. First, we aim to identify howmaternal adaptation to pregnancy conveys the advantageous or disadvantageous consequencesfor maternal health in individuals with MS or during influenza infection. Second, we aim to identifyhow a challenged maternal adaptation to pregnancy in response to prenatal stress or medicationwith acetaminophen or steroids is disadvantageous for fetal immune development and postnatalimmunity of the offspring. The concept of these aims is illustrated in Figure 1. We haveestablished relevant mouse models mirroring the respective immune diseases in humans. Wealso have access to pregnant women and - eventually - their children in order to translate findingsfrom mouse models into clinical relevance and vice versa. This now provides the platform onwhich we will be able to address our aims. Expected insights will lay the foundation for biomarkerdiscovery and offer opportunities for interventions to ameliorate adverse immune responses inhumans.