An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life.
An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life.
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DOI：
10.1038/s41467-023-44178-y
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发表时间：
2024-01-23
影响因子：
16.6
通讯作者：
Tsatsanis, Christos
中科院分区：
文献类型：
--
作者：
Vergadi, Eleni;Kolliniati, Ourania;Lapi, Ioanna;Ieronymaki, Eleftheria;Lyroni, Konstantina;Alexaki, Vasileia Ismini;Diamantaki, Eleni;Vaporidi, Katerina;Hatzidaki, Eleftheria;Papadaki, Helen A.;Galanakis, Emmanouil;Hajishengallis, George;Chavakis, Triantafyllos;Tsatsanis, Christos
中性粒细胞储备有限与新生儿感染的易感性有关，然而，中性粒细胞动力学在生命早期感染中的调节仍知之甚少。在这里，我们发现发育内皮基因座 (DEL-1) 在新生儿中升高，通过支持紧急粒细胞生成，对于新生儿多种微生物败血症的生存至关重要。脓毒症 DEL-1 缺陷的新生小鼠骨髓中的骨髓偏向性多能祖细胞和粒细胞-巨噬细胞祖细胞数量较少，导致中性粒细胞减少、菌血症严重和死亡率增加；通过 DEL-1 管理可以修复的缺陷。在新生儿脓毒症中观察到的高 IL-10/IL-17A 比率维持组织 DEL-1 表达，因为 IL-10 上调，而 IL-17 下调 DEL-1。一致地，血清IL-10/IL-17A比值高的脓毒症成人和新生儿患者的血清DEL-1和血液中性粒细胞升高，而血清DEL-1高的脓毒症患者的死亡率较低。因此，IL-10/DEL-1 轴支持紧急粒细胞生成，预防中性粒细胞减少症并促进败血症患者的早期生存。中性粒细胞在应对感染方面发挥着关键作用，新生儿和幼儿中可用中性粒细胞的限制可能会影响对感染（包括败血症）的反应。在此，作者确定 IL-10/DEL-1 轴参与新生儿的紧急粒细胞生成，并提出与脓毒症早期生存的联系。
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. Neutrophils play critical roles in response to infection, and the limit of available neutrophils in neonates and young infants can impact responses to infections, including sepsis. Here the authors identify that the IL-10/DEL-1 axis is involved in emergency granulopoiesis in neonates and suggest a link to sepsis survival in early life.
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