Abstract
Neutrophils, a key component of the innate immune system, undergo an acute surge in peripheral blood within the first day of life in mammalian neonates, yet the origin of this surge has remained elusive. In this study, we identify the fetal liver as the primary reservoir driving the postnatal neutrophil surge. In rat neonates, peripheral neutrophil counts rose significantly by 6 h after birth, a change not explained by a release from the bone marrow. Examination of fetal tissues revealed that neutrophils accumulate in the liver during late gestation in a granulocyte colony-stimulating factor (G-CSF)-dependent manner. Following delivery, both rat and mouse neonates displayed a rapid depletion of liver neutrophils within 12 h. Transcriptomic profiling of murine liver neutrophils at 3 h postpartum uncovered upregulation of Nos2 (encoding inducible nitric oxide synthase, iNOS). Pharmacological inhibition of NOS activity in rat pups significantly attenuated the magnitude of the postnatal neutrophil surge. Together, these findings reveal a previously unrecognized developmental program in which the fetal liver serves as the source of neutrophils that are mobilized immediately after birth, a mechanism that may underlie the diminished neutrophil response observed in preterm infants.