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

在过去的几十年里，人们对怀孕的母体免疫和内分泌适应有了更好的理解。这种适应创造了一个耐受性的生态位，在这个生态位中，同基因胎儿可以成功发育到足月。随之而来的是，这种适应对产妇健康既有好处，也有坏处。它可能会改善母体自身免疫性疾病的活动性，如多发性硬化症(MS)，但会增加感染的严重性，如流感。此外，怀孕期间母体适应的挑战可能会对孩子晚年的健康造成不利影响，例如免疫力低下，患慢性免疫性疾病的风险增加。产前的挑战包括产前压力感知和药物治疗。到目前为止，参与调节这些临床相关利弊的途径的跨学科开发仍然在很大程度上被忽视。这种忽视归因于医学领域之间的交流普遍有限。在这一合作计划中，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)和莱布尼茨实验病毒学研究所Heinrich-Pette-Institute的严格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，我们的目标是确定在多发性硬化症患者或流感感染期间，母亲对怀孕的适应如何传递对母亲健康有利或不利的结果。其次，我们的目标是确定孕妇因产前压力或服用对乙酰氨基酚或类固醇药物而面临的怀孕适应挑战如何对胎儿免疫发育和后代的出生后免疫不利。这些目标的概念如图1所示。我们已经建立了相关的小鼠模型，反映了人类各自的免疫疾病。我们还可以接触到孕妇，并最终接触到她们的孩子，以便将小鼠模型的发现转化为临床意义，反之亦然。这现在提供了一个平台，我们将能够在这个平台上实现我们的目标。预期的洞察力将为生物标志物的发现奠定基础，并为干预改善人类的不良免疫反应提供机会。

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.