adverse outcome pathway (AOP); developmental immunotoxicity (DIT); human immune system development; new approach methodologies (NAMs); physiological map (PM); systems biology; Animals; Humans; Immune System; Immunoinformatics; Immunology and Allergy; Immunology
Abstract :
[en] Human immune system development is established through a sequence of tightly regulated processes occurring across multiple embryonic and fetal organs. Despite extensive research, our mechanistic understanding still relies largely on animal models, which often lack translational precision for human biology. This gap is particularly relevant for developmental immunotoxicity (DIT), where early-life exposure to environmental contaminants such as dioxins, PCBs, and PFAS has been associated with long-term immune dysfunction, including reduced vaccine responsiveness in children. To address this need, we created the Human Immune System Development Map (HIDmap), a curated, findability, accessibility, interoperability, and reusability (FAIR)-compliant digital resource that systematically captures prenatal immune ontogeny. The HIDmap integrates literature-derived data into a modular, three-layered structure linking anatomical niches, cell migration, and differentiation trajectories across 24 organs. Implemented in the MINERVA (Molecular Interaction NEtwoRks VisuAlization) platform, the HIDmap allows interactive exploration of developmental processes and molecular markers relevant to immune function. By embedding the HIDmap within the Adverse Outcome Pathway (AOP) framework, we constructed a putative AOP to demonstrate how the map can help to connect molecular initiating events related to environmental exposures - such as Aryl hydrocarbon receptor (AhR) activation - to downstream immunological key events and adverse outcomes. This resource offers a human-centered foundation for curating and visualizing human developmental immunobiology and may support the future development of predictive in vitro New Approach Methodologies (NAMs). In the future, the HIDmap may contribute to the identification of critical windows of susceptibility and support the advancement of mechanism-based, animal-free approaches in developmental immunotoxicology.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Spruck, Christiane; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany
Maia Ladeira, Luiz Carlos ; Université de Liège - ULiège > GIGA > GIGA Molecular & Computational Biology - Biomechanics Research Unit
Kuchovska, Eliska; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany
Ostaszewski, Marek; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
de Caro, Emilia Rita; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany
Corsini, Emanuela; Department of Pharmacological and Biomolecular Sciences ‘Rodolfo Paoletti’, Università degli Studi di Milano, Milan, Italy
Geris, Liesbet ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique ; Skeletal Biology and Engineering Research Center, Katholieke Universiteit (KU) Leuven, Leuven, Belgium ; Biomechanics Section, Department of Mechanical Engineering, Katholieke Universiteit (KU) Leuven, Leuven, Belgium
Staumont, Bernard ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique
Fayyaz, Susann; Clariant Produkte (Deutschland) GmbH, Frankfurt am Main, Germany
Li, Qiang; Clariant Produkte (Deutschland) GmbH, Frankfurt am Main, Germany
Grimm, Fabian; Clariant Produkte (Deutschland) GmbH, Frankfurt am Main, Germany
Fritsche, Ellen; DNTOX GmbH, Duesseldorf, Germany ; SCAHT - Swiss Centre for Applied Human Toxicology, Basel, Switzerland ; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
Koch, Katharina; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany ; DNTOX GmbH, Duesseldorf, Germany
Tigges, Julia; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany
The author(s) declared that this work received funding from Clariant Produkte (Deutschland) GmbH. The funder was involved in the review and approval of the final manuscript.The author(s) declared that financial support was received for this work and/or its publication. The work was funded by the IUF - Leibniz Research Institute for Environmental Medicine. This work also received funding from the European Research Council under the European Union\u2019s Horizon 2020 Framework Program (H2020/2014-2021)/ERC grant agreement No 772418 (INSITE).
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