Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity.

ABSTRACT: The long-term impact of systemic hypoxia resulting from acute respiratory distress syndrome (ARDS) on the function of short-lived innate immune cells is unclear. We show that patients 3-6 months after recovering from ARDS have persistently impaired circulating neutrophil effector functions and an increased susceptibility to secondary infections. These defects are linked to a widespread loss of the activating histone mark H3K4me3 in genes that are crucial for neutrophil activities. By studying healthy volunteers exposed to altitude-induced hypoxemia, we demonstrate that oxygen deprivation alone causes this long-term neutrophil reprogramming. Mechanistically, mouse models of systemic hypoxia reveal that persistent loss of H3K4me3 originates in proNeu and preNeu progenitors within the bone ma

SUBMITTER: Sanchez-Garcia MA 

PROVIDER: S-EPMC12571872 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature