Research at the UKE?
DE
Feto-maternal immunology
We aim to understand the immune system during pregnancy in order to improve maternal and offspring’s health.
“We aim to understand the immune system during pregnancy in order to improve maternal and offspring’s health.”
Prof. Dr. Petra Arck
Project details and goals
Determinants of successful reproduction have emerged over millions of years in order to ensure survival of mammalian species. We utilize pre-clinical models and seek to translate resulting insights into the comprehensive evaluation of large human pregnancy studies with known outcomes and corresponding bio-samples. Our research also serves as a blueprint to inform multiple areas in the field of immunology, such as infection and autoimmunity.
Current projects
Long-term programming of sex differences in immunity by prenatal exposure to stress
Prenatal adverse environments including the exposure to stress adversely program immunity later in life. Hereby, significant sex differences in childhood and during adult life have been observed. We here investigate how fetal exposure to prenatal glucocorticoid surges differentially modulates long-term immunity later in life of male and female offspring. This project is embedded in the RU5068
Further information:
Prediction of preterm birth - prevention of inequality among children
Each year, approx. 15 million babies worldwide are born prematurely, before gestation week 37. These children have an increased risk to die during their first year of life and to develop health problems. Despite continuous progress made in the field of preventive medicine over the last decades, the options to predict preterm birth are still very poor. Therefore, it is the goal of our project to characterize biological signatures that are predictive for preterm birth at a time point during pregnancies when no risk can be foreseen. Such knowledge will then inform future prenatal care and allows to identify pregnancies at risk for preterm birth by clinical routine screening. This project is funded with the Next Generation Partnerships Initiative of the BMBF/Excellence Initiative Hamburg
Further information:
Sexual and Reproductive Health in Overweight and Obesity
Overweight and obesity currently affects one third of the population in industrialized countries, including women and men during their reproductive years. During pregnancy, overweight and obesity significantly increases the risk for pregnancy complications and also interferes with fetal development and future health of the children. We are a member of the Interdisciplinary Junior Scientist Research Centre on Reproductive Health. In this centre, Medical and Clinician scientists are promoted to pursue research projects aiming to mitigate the overweight/obesity related health risks during reproduction. This project is funded by the BMBF.
ImplantEU
Embryo implantation in a receptive uterus is critical for mammalian reproduction, yet remains poorly understood. This challenge is particularly significant in human health, as up to two-thirds of human pregnancies are lost due implantation failure. Much remains unknown about the molecular pathways and regulatory mechanisms of embryo-endometrial/decidual interactions in humans. We here aim to develop an epigenetic blueprint of immune cells subsets during implantation. This project is embedded in a Doctoral Networks funded by Horizon 2023 (Website is currently being created).
Development of a web-based system to document scientific experiments and ensure animal welfare
Biomedical research relies heavily on laboratory animals, but guidelines for documenting animal experiments under the Animal Welfare Act are poorly defined. To address this, we aim to develop a comprehensive documentation system that complies with the law and integrates artificial intelligence to detect stress in laboratory animals. Funded by the Calls4Transfer program (https://callsfortransfer.de), this innovation will significantly contribute to legally compliant and optimized documentation of animal experiments while improving animal welfare.
Early determinants of health and diseases
The developmental trajectory of a child is shaped by a multitude of internal and external factors to which the mother is exposed to during pregnancy. These factors contribute to both the susceptibility to illnesses and the emergence of developmental disorders. As a member of the German Center for Child and Adolescent Health (https://dzkj.org), we aim to delineate the health hazards arising from the interplay between inherent predispositions and the dynamic environmental landscape. Additionally, we endeavour to elucidate the risk and resilience elements, and unravel the intricate mechanisms underpinning the onset of prevalent childhood diseases.
Publications 2025
Urbschat C, Arck PC. Semin Immunopathol. 2025 Aug 6;47(1):33.
Abstract
Microchimerism refers to the presence of a small number of foreign, mostly conspecific, cells within an individual. Decades ago, the pioneering researcher in this field faced significant skepticism because the prevailing view was that foreign cells could not survive for long periods inside the host. Today, the existence of microchimerism is widely accepted. Nonetheless, the field still lacks a clear quantitative definition, especially in mammals. There is no universally agreed threshold or precise boundary that qualifies as microchimerism. Additionally, distinguishing microchimerism from other types, such as ‘macrochimerism’ or ‘multichimerism,’ remains difficult. Although its functional role is largely an unresolved mystery, recent studies show that chimerism plays an essential role during immune and neurocognitive development. Here, we compile a comprehensive collection of articles highlighting recent advances across different areas of chimerism research and summarize the known types of chimerism and their modes of acquisition.
Thiele K, Urbschat C, Riquelme JIA, Ahrendt LS, Wöhrle R, Schepanski S, Eckert JJ, Becht E, Qi M, Alawi M, Becker M, Gagliani N, Mittrücker HW, Diemert A, Arck PC. Nat Commun. 2025 Jul 15;16(1):6522.
Abstract
Subsequent pregnancies are generally less prone to obstetric complications. A successful pregnancy outcome requires pivotal immunological adaptation to ensure immune tolerance towards the foetus. Thus, the lower risk for pregnancy complication during subsequent pregnancies may be attributable to immune memory mounted during first pregnancies. Here we identify higher frequencies of fetal-antigen-specific CD4+ regulatory T (Treg) cells both postpartum and in subsequent pregnancies in mice which are partly originating from trans-differentiated Th17 cells. Our functional experiments demonstrate that these CD4+ Treg cells have memory functions (CD4+ mTreg) and account for an improved fetal development and pregnancy outcome, also during adverse conditions, such as gestational sound stress. Using a high-throughput single-cell quantification method, we identify candidate markers for the detection of CD4+ mTreg cells, which include CXCR4 and CD274. Our findings thus contribute to the improved understanding of pregnancy-induced immune memory and foster the identification of immune targets aiming to reduce the risk for immune-mediated pregnancy complications.
Wiemers P, Graf I, Addo MM, Arck PC, Diemert A. Semin Immunopathol. 2025 Apr 24;47(1):25.
Abstract
Infectious diseases have threatened individuals and societies since the dawn of humanity. Certain population groups, including pregnant women, young children and the elderly, are particularly vulnerable to severe infections. Over the past few centuries, advances in medical standards and the availability of vaccines have reduced infection-related mortality and morbidity rates in industrialized countries. However, the global rise in temperatures and increased precipitation present a new challenge, facilitating the broader distribution of disease vectors, such as mosquitoes, bugs and ticks, to higher altitudes and latitudes. Consequently, epidemic and pandemic outbreaks associated with these vectors, such as Zika, West Nile, dengue, yellow fever, chikungunya and malaria, are increasingly impacting diverse populations. This review comprehensively examines how infections associated with climate change disproportionately affect the health and well-being of pregnant women and their unborn children. There has been a noticeable emergence of vector-borne diseases in Europe. Consequently, we stress the importance of implementing measures that effectively protect pregnant women from these increasing infections globally and regionally. We advocate for initiatives to safeguard pregnant women from these emerging threats, beginning with enhanced education to raise awareness about the evolving risks this particularly vulnerable population faces.
Padula AM, Salihovic S, Zazara DE, Diemert A, Arck PC. Environ Res. 2025 Apr 1;270:120976.
Abstract
Background: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals posing environmental and health risks. Impact on the human immune system is of particular concern, especially during fetal immune development. Alterations to fetal immune development can impact immunity later in life, e.g., the response to vaccines and pathogens.
Objectives: This study investigated the association between PFAS concentrations in healthy pregnant women from Hamburg, Germany, and antibody levels to routine vaccines in childhood and occurrence of childhood infections.
Methods: Mid-pregnancy serum samples from 152 mothers-child pairs were analyzed for 18 PFAS compounds, and antibody levels to measles, mumps, rubella, diphtheria, and tetanus were assessed at age 5. Maternal questionnaires provided data on childhood infections each year at age 1–5. Linear and Poisson regression models were adjusted for maternal age, education, parity, and breastfeeding duration. Weighted quantile sum (WQS) regression was used to assess the PFAS mixture.
Results: Higher PFAS concentrations were associated with lower antibody titers at age 5 years, particularly for mumps, tetanus, diphtheria, and rubella. Several PFAS were also linked to increased childhood infections, especially respiratory infections, during ages 3 and 4 years. WQS regression revealed a negative association between combined PFAS and tetanus titers.
Conclusions: Maternal PFAS concentrations during pregnancy are inversely associated with antibody levels in children and positively associated with increased childhood infections, notably respiratory infections. These findings underscore the importance of understanding environmental exposures' impact on immune responses and call for continued monitoring of PFAS in both the environment and human populations to mitigate health risks.
Previous publications
Yüzen D, Graf I, Tallarek AC, Hollwitz B, Wiessner C, Schleussner E, Stammer D, Padula A, Hecher K, Arck PC, Diemert A. Increased late preterm birth risk and altered uterine blood flow upon exposure to heat stress. EBioMedicine. 2023 Jul;93:104651.
Summary
Background: Climate change, in particular the exposure to heat, impacts on human health and can trigger diseases. Pregnant people are considered a vulnerable group given the physiological changes during pregnancy and the potentially long-lasting consequences for the offspring. Evidence published to date on higher risk of pregnancy complicationsupon heat stress exposure are from geographical areas with high ambient temperatures. Studies from geographic regions with temperate climates are sparse; however, these areas are critical since individuals may be less equipped to adapt to heat stress. This study addresses a significant gap in knowledge due to the temperature increase documented globally.
Methods: Birth data of singleton pregnancies (n = 42,905) from a tertiary care centre in Hamburg, Germany, between 1999 and 2021 were retrospectively obtained and matched with climate data from the warmer season (March to September) provided by the adjacent federal meteorological station of the German National Meteorological Service to calculate the relative risk of heat-associated preterm birth. Heat events were defined by ascending temperature percentiles in combination with humidity over exposure periods of up to 5 days. Further, ultrasound data documented in a longitudinal prospective pregnancy cohort study (n = 612) since 2012 were used to identify pathophysiological causes of heat-induced preterm birth.
Findings: Both extreme heat and prolonged periods of heat exposure increased the relative risk of preterm birth (RR: 1.59; 95% CI: 1.01–2.43; p = 0.045; RR: 1.20; 95% CI: 1.02–1.40; p = 0.025). We identified a critical period of heat exposure during gestational ages 34–37 weeks that resulted in increased risk of late preterm birth (RR: 1.67; 95% CI: 1.14–1.43; p = 0.009). Pregnancies with a female fetus were more prone to heat stress-associated preterm birth. We found heat exposure was associated with altered vascular resistancewithin the uterine artery.
Interpretation: Heat stress caused by high ambient temperatures increases the risk of preterm birth in a geographical region with temperate climate. Prenatal routine care should be revised in such regions to provide active surveillance for women at risk.
Schepanski S, Chini M, Sternemann V, Urbschat C, Thiele K, Sun T, Zhao Y, Poburski M, Woestemeier A, Thieme MT, Zazara DE, Alawi M, Fischer N, Heeren J, Vladimirov N, Woehler A, Puelles VG, Bonn S, Gagliani N, Hanganu-Opatz IL, Arck PC. Nat Commun. 2022 Aug 5;13(1):4571.
Abstract
Life-long brain function and mental health are critically determined by developmental processes occurring before birth. During mammalian pregnancy, maternal cells are transferred to the fetus. They are referred to as maternal microchimeric cells (MMc). Among other organs, MMc seed into the fetal brain, where their function is unknown. Here, we show that, in the offspring’s developing brain in mice, MMc express a unique signature of sensome markers, control microglia homeostasis and prevent excessive presynaptic elimination. Further, MMc facilitate the oscillatory entrainment of developing prefrontal-hippocampal circuits and support the maturation of behavioral abilities. Our findings highlight that MMc are not a mere placental leak out, but rather a functional mechanism that shapes optimal conditions for healthy brain function later in life.
Stelzer IA, Urbschat C, Schepanski S, Thiele K, Triviai I, Wieczorek A, Alawi M, Ohnezeit D, Kottlau J, Huang J, Fischer N, Mittrücker HW, Solano ME, Fehse B, Diemert A, Stahl FR, Arck PC. NatCommun. 2021 Aug 4;12(1):4706.
Abstract
During mammalian pregnancy, immune cells are vertically transferred from mother to fetus. The functional role of these maternal microchimeric cells (MMc) in the offspring is mostly unknown. Here we show a mouse model in which MMc numbers are either normal or low, which enables functional assessment of MMc. We report a functional role of MMc in promoting fetal immune development. MMc induces preferential differentiation of hematopoietic stem cells in fetal bone marrow towards monocytes within the myeloid compartment. Neonatal mice with higher numbers of MMc and monocytes show enhanced resilience against cytomegalovirus infection. Similarly, higher numbers of MMc in human cord blood are linked to a lower number of respiratory infections during the first year of life. Our data highlight the importance of MMc in promoting fetal immune development, potentially averting the threats caused by early life exposure to pathogens.
Kinder JM, Stelzer IA, Arck PC, Way SS. Nat Rev Immunol. 2017 Aug;17(8):483-494.
Abstract
Immunological identity is traditionally defined by genetically encoded antigens, with equal maternal and paternal contributions as a result of Mendelian inheritance. However, vertically transferred maternal cells also persist in individuals at very low levels throughout postnatal development. Reciprocally, mothers are seeded during pregnancy with genetically foreign fetal cells that persist long after parturition. Recent findings suggest that these microchimeric cells expressing non-inherited, familially relevant antigenic traits are not accidental 'souvenirs' of pregnancy, but are purposefully retained within mothers and their offspring to promote genetic fitness by improving the outcome of future pregnancies. In this Review, we discuss the immunological implications, benefits and potential consequences of individuals being constitutively chimeric with a biologically active 'microchiome' of genetically foreign cells.
Engels G, Hierweger AM, Hoffmann J, Thieme R, Thiele S, Bertram S, Dreier C, Resa-Infante P, Jacobsen H, Thiele K, Alawi M, Indenbirken D, Grundhoff A, Siebels S, Fischer N, Stojanovska V, Muzzio D, Jensen F, Karimi K, Mittrücker HW, Arck PC*, Gabriel G*. Cell Host Microbe. 2017 Mar 8;21(3):321-333.
Abstract
Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8+ T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues.
Team
Prof. Dr. med. Petra Arck
Head
Dean’s office for Research
Project leader - Experimental Feto-Maternal Medicine
E-mail address:
