Ishiwata Ryo
Department of Physiology, National Defense Medical College, Tokorozawa City, Japan.
Exp Hematol. 2025 Aug;148:104798. doi: 10.1016/j.exphem.2025.104798. Epub 2025 May 9.
This review examined the dynamic development and unique characteristics of neutrophils during the perinatal period, a critical window when the immune system undergoes rapid reprogramming, based on the mouse studies. In the mouse fetal liver-the primary hematopoietic niche before birth-hematopoietic stem cells and progenitor cells expand in parallel, with granulocyte-monocyte progenitors preferentially differentiating into neutrophils during late gestation. This process, partly driven by granulocyte colony-stimulating factor (G-CSF), substantially increases the number of neutrophils, preparing the neonates for microbial challenges after birth. After birth, there is a surge in circulating neutrophils, likely due to the mobilization of neutrophils from the liver, followed by a microbiota-dependent activation of granulopoiesis in the bone marrow. In addition to their antimicrobial functions, neonatal neutrophils exhibit immunomodulatory characteristics, such as reduced proinflammatory signaling and diminished neutrophil extracellular trap formation. These traits may contribute to tolerance to the microbes and help mitigate excessive inflammation. Finally, unresolved issues related to the phenotypic diversity and precise physiological roles of neutrophils during the perinatal period are addressed, highlighting the need for further research.
基于小鼠研究，本综述探讨了围产期中性粒细胞的动态发育及独特特征，围产期是免疫系统经历快速重编程的关键时期。在小鼠胎儿肝脏（出生前主要的造血微环境）中，造血干细胞和祖细胞平行扩增，粒细胞-单核细胞祖细胞在妊娠后期优先分化为中性粒细胞。这一过程部分由粒细胞集落刺激因子（G-CSF）驱动，显著增加了中性粒细胞的数量，为新生儿出生后应对微生物挑战做好准备。出生后，循环中性粒细胞激增，可能是由于中性粒细胞从肝脏动员所致，随后骨髓中粒细胞生成受微生物群依赖的激活。除了抗菌功能外，新生儿中性粒细胞还表现出免疫调节特性，如促炎信号减少和中性粒细胞胞外陷阱形成减少。这些特性可能有助于对微生物的耐受，并有助于减轻过度炎症。最后，讨论了围产期中性粒细胞表型多样性和精确生理作用相关的未解决问题，强调了进一步研究的必要性。
