Institute for Immunology

Project description:

Balancing pathogen defence with maintaining tolerance to environmental antigens, such as food or commensals, in neonates is essential for survival and the establishment of life-long immune homeostasis. Instructed by environmental signals conventional dendritic cells (cDC) drive either T cell tolerance or immunity. We have recently uncovered an interferon (IFN)-γ-driven regulatory circuit in early life that relays dietary cues to spleen cDC1. Loss-of-function demonstrates that IFNγ-mediated STAT1-signaling induces an immunogenic maturation program in spleen cDC1 that instructs cDC1 to expand effector memory CD8⁺ T cells. This program emerges during weaning, when IFNγ production from lymphocytes rises, it occurs in germ-free mice and remains responsive to dietary intervention in adult mice. During the transition from breastfeeding to solid food at weaning, this circuit relays dietary information to spleen cDC1 to shape the effector phenotype of food-antigen specific CD8+ T cells in a feed-forward manner.

Continuing on from this work the proposed project investigates using perinatal in vivo and in vitro models, combined with genetic tools and feeding different diets, how this circuit influences the response to pathogens and allergens in particular in the lung and intestine.