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

Eleni Vergadi (), Ourania Kolliniati, Ioanna Lapi, Eleftheria Ieronymaki, Konstantina Lyroni, Vasileia Ismini Alexaki, Eleni Diamantaki, Katerina Vaporidi, Eleftheria Hatzidaki, Helen A. Papadaki, Emmanouil Galanakis, George Hajishengallis, Triantafyllos Chavakis and Christos Tsatsanis
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Eleni Vergadi: University of Crete
Ourania Kolliniati: Institute of Molecular Biology and Biotechnology, IMMB, FORTH
Ioanna Lapi: Institute of Molecular Biology and Biotechnology, IMMB, FORTH
Eleftheria Ieronymaki: Institute of Molecular Biology and Biotechnology, IMMB, FORTH
Konstantina Lyroni: Institute of Molecular Biology and Biotechnology, IMMB, FORTH
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

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44178-y

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