Prenatal development of the immune system is orchestrated by cell-intrinsic programs guiding immune cell development and the generation of immunological niches in the context of organ development. These programs operate under the protected conditions of intrauterine life. 

Birth challenges immune system development

At the transition from intrauterine to postnatal life, the separation of mother and infant presents sudden and drastic challenges to these developmental programs. These challenges include environmental factors, changes in oxygen tension, acquisition of the individual microbiota, metabolic changes and enteral nutrient exposure. This results in major alterations in the tissue microenvironment, contributing to adaptive changes in cellular immunity that occur in parallel to the replacement of fetal cells by “postnatal” cells. 

It is therefore not surprising that aberrant perinatal development, such as premature birth or perinatal infection, has severe consequences for immediate and long-term tissue integrity and protection, microbiota composition and immune homeostasis. However, the key parameters regulating immune cell adaption during the normal or aberrant perinatal period remain poorly defined.

Preprogrammed and responsive development of perinatal immunity

PILOT focuses on the analysis of the preprogrammed development, the impact of the birth transition and the impact on postnatal cues on immune cell development. 

• We study particular anatomical niches, such as barrier tissues of intestine and lung, the dermis and the placenta, where structures with discrete functions meet. 
• Due to the recent development of multi-dimensional analytical tools, e.g. high-resolution tissue imaging, single-cell transcriptome and epigenome analysis, and fate mapping that reliably work with minute cell numbers, these niches can now be studied in the fetal/neonatal host in an unprecedented fashion. 
• With the help of unbiased clustering of data and machine learning, we are developing novel algorithms to advance our understanding of how the complex challenges of perinatal transition are integrated and translated into maintenance of cellular immunity. 

Identification of key parameters shaping immunity in early life will support the ultimate goal of the PILOT consortium: steering immunity for a better start and for long-term health.