Sleep Deprivation Activates a Conserved Lactate-H3K18la-RORα Axis Driving Neutrophilic Inflammation Across Species.

ABSTRACT: Sleep deprivation critically disrupts physiological homeostasis, impairing development, metabolic balance, and immune regulation, with excessive neutrophil activation being a hallmark consequence. However, the molecular mechanisms underlying sleep deprivation-induced neutrophilic inflammation remain elusive. Here, it is shown that acute sleep deprivation in mice triggers neutrophil hyperactivation, resulting in aberrant peripheral accumulation and a systemic cytokine storm. Mechanistically, this pathology is driven by metabolic dysregulation, specifically, increased glycolytic flux, which elevates tissue lactate levels and enhances histone H3K18 lactylation. Through H3K18 lactylation-specific CUT&Tag profiling, pronounced lactylation enrichment is identified at the promoter of the Rorα gen

SUBMITTER: Zhou R 

PROVIDER: S-EPMC12520482 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature