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An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life

Author

Listed:
  • Eleni Vergadi

    (University of Crete
    Institute of Molecular Biology and Biotechnology, IMMB, FORTH)

  • Ourania Kolliniati

    (Institute of Molecular Biology and Biotechnology, IMMB, FORTH
    University of Crete)

  • Ioanna Lapi

    (Institute of Molecular Biology and Biotechnology, IMMB, FORTH
    University of Crete)

  • Eleftheria Ieronymaki

    (Institute of Molecular Biology and Biotechnology, IMMB, FORTH
    University of Crete)

  • Konstantina Lyroni

    (Institute of Molecular Biology and Biotechnology, IMMB, FORTH
    University of Crete)

  • Vasileia Ismini Alexaki

    (Technische Universität Dresden)

  • Eleni Diamantaki

    (University of Crete)

  • Katerina Vaporidi

    (University of Crete)

  • Eleftheria Hatzidaki

    (University of Crete)

  • Helen A. Papadaki

    (University of Crete)

  • Emmanouil Galanakis

    (University of Crete)

  • George Hajishengallis

    (University of Pennsylvania)

  • Triantafyllos Chavakis

    (Technische Universität Dresden)

  • Christos Tsatsanis

    (Institute of Molecular Biology and Biotechnology, IMMB, FORTH
    University of Crete)

Abstract

The limited reserves of neutrophils are implicated in the susceptibility to infection in neonates, however the regulation of neutrophil kinetics in infections in early life remains poorly understood. Here we show that the developmental endothelial locus (DEL-1) is elevated in neonates and is critical for survival from neonatal polymicrobial sepsis, by supporting emergency granulopoiesis. Septic DEL-1 deficient neonate mice display low numbers of myeloid-biased multipotent and granulocyte-macrophage progenitors in the bone marrow, resulting in neutropenia, exaggerated bacteremia, and increased mortality; defects that are rescued by DEL-1 administration. A high IL-10/IL-17A ratio, observed in newborn sepsis, sustains tissue DEL-1 expression, as IL-10 upregulates while IL-17 downregulates DEL-1. Consistently, serum DEL-1 and blood neutrophils are elevated in septic adult and neonate patients with high serum IL-10/IL-17A ratio, and mortality is lower in septic patients with high serum DEL-1. Therefore, IL-10/DEL-1 axis supports emergency granulopoiesis, prevents neutropenia and promotes sepsis survival in early life.

Suggested Citation

  • Eleni Vergadi & Ourania Kolliniati & Ioanna Lapi & Eleftheria Ieronymaki & Konstantina Lyroni & Vasileia Ismini Alexaki & Eleni Diamantaki & Katerina Vaporidi & Eleftheria Hatzidaki & Helen A. Papadak, 2024. "An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44178-y
    DOI: 10.1038/s41467-023-44178-y
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