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

KFO 296：胎儿-母体免疫串扰：对母体和后代健康的影响

• 批准号: 255154572
• 金额: --
• 依托单位: Leibniz-Institut für Virologie (LIV)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/255154572?language=en
• 关键词: KFO; 296; Feto; maternal; immune

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.

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理解。这种适应创造了一个耐受性生态位，在这个生态位中，半同种异体胎儿可以成功发育到足月。与此同时，这种适应对产妇健康有利也有弊。它可以改善母体自身免疫性疾病的活动，如多发性硬化症（MS），但增加感染的严重性，如流感。此外，母亲在怀孕期间的适应能力受到挑战，如免疫力差和患慢性免疫性疾病的风险增加，可能会对儿童以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。迄今为止，跨学科开发的途径参与调解这些临床相关的优势和劣势，孕产妇和儿童的健康仍然在很大程度上被忽视。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克服了这一局限性。作为一个严格的跨学科临床研究单位，我们在汉堡大学医学院（UKE）和海因里希-佩特研究所（Leibniz Institute for Experimental Virology）的基础上组建，现在我们寻求共同解决两个关键目标。首先，我们的目标是确定母亲对怀孕的适应如何传达MS患者或流感感染期间对母亲健康有利或不利的后果。其次，我们的目标是确定母亲对产前压力或对乙酰氨基酚或类固醇药物的适应性如何对胎儿免疫发育和后代的出生后免疫力不利。这些目标的概念如图1所示。我们已经建立了反映人类相应免疫疾病的相关小鼠模型。我们还可以接触孕妇，最终接触她们的孩子，以便将小鼠模型的发现转化为临床相关性，反之亦然。这为我们实现目标提供了一个平台。预期的见解将为生物标志物的发现奠定基础，并为改善人类不良免疫反应的干预措施提供机会。