Authors
Doğuş Altunöz, Ramin Shakiba, Kaushikk Ravi Rengarajan, Hamsa Narasimhan, Nikos E Papaioannou, Sadiq Nasrah, Jessica Vetters, Maria L Richter, María Parra Reyes, Nadine Nuschele, Denise Messerer, Sabine Schwamberger, Andreas Goschin, Dimitrios Starfas, Melanie Schmid, Tobias Straub, Michele Proietti, Katrin Böttcher, Maria Colomé-Tatché, Dirk Haller, Jan P Böttcher, Stephanie C Ganal-Vonarburg, Sophie Janssens, Christian Schulz, Anne B Krug, Barbara U Schraml
Published in
Nature communications. Volume 17. Issue 1. Aug 04, 2026. Epub Aug 04, 2026.
Abstract
Maintaining a balanced immunity between pathogen defense and tolerance to environmental antigens in neonates is essential for survival and the establishment of life-long immune homeostasis. Instructed by environmental signals, type 1 conventional dendritic cells (cDC1) contribute to both processes but how the balance may be achieved is unclear. Here, we uncover an interferon (IFN)γ-driven regulatory circuit in early life that relays dietary cues to spleen cDC1. IFNγ-mediated STAT1-signaling induces an immunogenic maturation program in spleen cDC1 that enables them to shape the effector differentiation of antigen-experienced effector memory CD8⁺ T cells. This cDC1 program emerges during the transition from breastfeeding to solid food at weaning, occurs in germ-free mice, and remains operative to dietary intervention in adult mice. At weaning, this IFNγ signal enables spleen cDC1 to shape the effector phenotype of food-antigen-specific CD8+ T cells in a feedforward manner, thereby recalibrating the developing T cell pool. Our findings identify diet as a modifiable cue that can tune systemic cDC1-mediated immunity, opening new opportunities to steer immune responses during early life and beyond.
PMID:
42552313
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.
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