Peri-weaning, diet-induced activation of an IFNγ-mediated regulatory circuit promotes cDC1 maturation and CD8+ T cell differentiation
- 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
2026-08-04
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.