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

• Subject Area: Medicine
• Term: from 2015 to 2023
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255154572

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.

• DFG Programme: Clinical Research Units

Projects

• Congenital cytomegalovirus infection: identification of factors determining vertical transmission and clinical outcome of infected neonates (Applicants Brune, Wolfram ;  Stahl, Ph.D., Felix )
• Coordination Funds (Applicant Arck, Petra Clara )
• Coordination of the prospective pregnancy cohort PRINCE (Prenatal Identification of Children’s Health) (Applicants Diemert, Anke ;  Fehse, Boris ;  Hecher, Kurt ;  Muntau, Ania Carolina ;  Singer, Dominique ;  Stock, Philippe ;  Tolosa, Eva ;  Zapf, Antonia )
• Diet during pregnancy and maternal obesity: effects on the function of maternal TH17 and Treg cells and on subsequent offspring health (Applicants Bonn, Stefan ;  Gagliani, Ph.D., Nicola )
• Hormonal modulation of the Type I Interferon response during pregnancy: implications for maternal health and disease (Applicant Altfeld, Marcus )
• Influenza during pregnancy: The emergence of highly virulent H1N1 influenza virus strains and consequences for maternal and offspring’s health (Applicants Arck, Petra Clara ;  Gabriel, Gülsah ;  Mittrücker, Hans-Willi )
• Mechanisms of prenatal glucocorticoid-induced changes on the offspring's immune system (Applicant Tolosa, Eva )
• Prenatal acetaminophen medication affects offspring’s immunity. (Applicant Tiegs, Gisa )
• Prenatal stress challenge in mice: the role of vertically transmitted maternal glucocorticoids and immune cells in modulating offspring‘s immunity (Applicants Arck, Petra Clara ;  Zazara, Dimitra )
• T cell diversity and plasticity during pregnancy and their contribution to multiple sclerosis disease activity (Applicants Friese, Manuel A. ;  Gold, Stefan M. )

• Spokesperson: Professorin Dr. Petra Clara Arck
• Leader: Professorin Dr. Eva Tolosa
• Project Heads: Professor Dr. Marcus Altfeld; Professor Dr. Heiko Becher; Professor Dr. Stefan Bonn; Professor Dr. Wolfram Brune; Professorin Madeleine Bunders, Ph.D.; Professorin Dr. Anke Diemert; Professor Dr. Boris Fehse; Professor Dr. Manuel A. Friese; Professorin Dr. Gülsah Gabriel; Professor Nicola Gagliani, Ph.D.; Professor Dr. Stefan M. Gold; Professor Dr. Kurt Hecher; Professor Dr. Hans-Willi Mittrücker; Professorin Dr. Ania Carolina Muntau; Professor Dr. Dominique Singer; Professorin Dr. Maria Emilia Solano; Professor Felix Stahl, Ph.D.; Professor Dr. Philippe Stock; Professorin Dr. Gisa Tiegs