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<p>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<sup>+</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • 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

摘要

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.