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However, the molecular mechanisms underlying sleep deprivation\u2010induced 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\u2010specific CUT&amp;Tag profiling, pronounced lactylation enrichment is identified at the promoter of the\n                    <jats:italic>Ror\u03b1<\/jats:italic>\n                    gene, directly activating its transcription. Genetic ablation of\n                    <jats:italic>Ror\u03b1<\/jats:italic>\n                    or pharmacological inhibition of glycolysis attenuate neutrophil recruitment and mitigated inflammation in sleep\u2010deprived zebrafish. Strikingly, this metabolic\u2012epigenetic axis is evolutionarily conserved, as demonstrated by the recapitulation of key findings in diurnal zebrafish and pigs. The study reveals a lactate\u2010H3K18 lactylation\u2010Ror\u03b1 signaling cascade that links sleep deprivation to immune dysregulation, suggesting actionable targets for combating sleep\u2010related inflammatory disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.202504028","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:00:18Z","timestamp":1753092018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Sleep Deprivation Activates a Conserved Lactate\u2010H3K18la\u2010ROR\u03b1 Axis Driving Neutrophilic Inflammation Across Species"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4309-6244","authenticated-orcid":false,"given":"Ren","family":"Zhou","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Anhui Agricultural University  Hefei 230036 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