Early Postnatal Immune Control – Local regulation of Dendritic Cell Function

• Applicant: Professorin Dr. Barbara Schraml
• Subject Area: Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550925575

Early immune balance is essential for survival and the establishment of life-long immune homeostasis. Tissue microenvironments drive immune cell function but in early life tissues are still developing. We aim to define how the developing tissue microenvironment contributes to creating immune balance. Conventional dendritic cells (cDC) are versatile controllers of immunity that in neonates are qualitatively distinct from adults. I have found that environmental signals, rather than ontogeny, imprint the functions of spleen cDC2 in early and adult life. Preliminary data show that spleen cDC function changes around weaning. During weaning the organism transitions from breast milk to solid food and host-microbial cross-talk is needed to establish lasting immune homeostasis. I propose that cDC function is actively regulated in developing tissues and in response to macroenvironmental factors associated with weaning to create precise immune balance. Thus, I have identified a unique situation in early life spleen to address a fundamental biological question, namely to what extent dendritic cell function is plastic within changing tissue microenvironments. We will use innovative longitudinal transcriptional profiling of stromal cells and high-end microscopy to define the cDC niche with age and to identify factors that mediate cDC-stromal cell communication. Using stromal cell specific genetic deletion of candidate factors, we will define how cDC-stromal cell communication shapes cDC function with age. Defining how the developing tissue niche and weaning shape cDC function will provide novel insights into immune development with therapeutic implications relevant to immunology and medicine.

• DFG Programme: Research Grants