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TRR 359:  Perinatal Development of Immune Cell Topology

Subject Area Medicine
Biology
Term since 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 491676693
 
Prenatal development of the immune system is orchestrated by cell-intrinsic programs that guide immune cell differentiation and instruct complex immunological solutions during organ development. At birth, separation from the mother triggers sudden, drastic challenges for the infant’s immune system, such as acquisition of microbiota, changes in oxygen tension and metabolism, and enteral nutrient exposure. The external stimuli and resultant alterations in tissue microenvironment are distinct for each organ and subanatomical site. Simultaneously, there is an influx of immune cells originating from definitive hematopoiesis. Aberrant perinatal immune development thus has severe consequences for tissue integrity and protection, microbiota composition and immune homeostasis. Yet the parameters regulating immune cell adaption during normal or aberrant perinatal development remain poorly defined. Tissue-specific information is limited and neonatal human samples are scarce. The proposed CRC TRR “Perinatal development of immune cell topology (PILOT)” aims to explore mechanisms that direct perinatal differentiation of immune cells and their cellular environment. PILOT will dissect how preprogrammed developmental traits and perinatal exogenous cues integrate to steer immune cell differentiation, establish immune homeostasis and provide immunity to infections. We will study subanatomical niches where structures with discrete functions meet, such as barrier tissues of intestine, lung and skin, and protected sites including the placenta. PILOT interlinks temporal and spatial aspects in two research areas. In Area A, “Response to exogenous cues”, the focus is on external factors that modulate immune cell repertoire development and drive diversification and adaptation of tissue-resident and circulating immune cells. Area B, “Preprogrammed development”, addresses cell-intrinsic programs that steer topology and function during perinatal immune cell development. Pioneering analytical tools, such as high-resolution imaging, single-cell transcriptome, epigenome and proteome analysis and in vivo fate mapping, will enable unique investigations of diverse and even small fetal and neonatal tissue niches. Using automated image analysis, unbiased data clustering and machine learning, PILOT will develop novel algorithms to elucidate how complex signals are integrated and translated to establish and maintain cellular immunity. These tools will be used not only in perinatal mouse and heterocellular in vitro models, but also in human neonatal biomaterial, thereby integrating translational perspectives into the consortium. Identification and modification of key parameters determining immunity around birth promises unique insights into how cellular immunity emerges through adaptation between host and environment on the global level, and microanatomically in the tissue. This will lay the foundation for PILOT’s ultimate goal: steering immunity for a better start and long-term health.
DFG Programme CRC/Transregios

Current projects

Applicant Institution Albert-Ludwigs-Universität Freiburg
Co-Applicant Institution Ludwig-Maximilians-Universität München
 
 

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