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Consequently, this study elucidates the neuroimmune mechanisms linking SD to ligature\u2010induced periodontitis (LIP) in mice and evaluates electroacupuncture (EA) as a novel adjunctive therapy. Screening analyses (ELISA, public databases, flow cytometry, immunofluorescence, etc.) identified pivotal roles of acetylcholine (ACh), \u03b17 nicotinic acetylcholine receptor (\u03b17nAChR), and acetylcholinesterase (AChE) in SD\u2010aggravated periodontitis with a decrease in ACh levels, down\u2010regulation of \u03b17nAChR on macrophages, and an increase in trigeminal ganglion\u2010derived AChE. Clinical validation in periodontitis patients with poor sleep (PSQI\u00a0\u2265\u00a05) confirmed this tripartite cholinergic imbalance. Ultimately, both in vivo and in vitro data demonstrated that EA inhibits M1 polarization while promoting M2 polarization of macrophages through \u03b17nAChR activation. Therefore, SD exacerbates periodontitis via the AChE\u2010ACh\u2010\u03b17nAChR axis\u2010mediated trigeminal\u2010periodontal neuroimmune pathway, whereas EA partially reverses this pathology by targeting macrophage \u03b17nAChR. These findings reveal new insights into the \u201coral\u2010brain axis\u201d in oral disease pathogenesis and provide novel therapeutic strategies for periodontitis patients with comorbid sleep disorders.<\/jats:p>","DOI":"10.1002\/advs.202500945","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T14:30:13Z","timestamp":1755181813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sleep Deprivation Aggravates Periodontitis Through Trigeminal\u2010Periodontal Neuroimmune Pathway Mediated by the AChE\u2010ACh\u2010\u03b17nAChR Axis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-5862","authenticated-orcid":false,"given":"Kehao","family":"Liu","sequence":"first","affiliation":[{"name":"College of Stomatology Chongqing Medical University  Chongqing 401147 P. R. 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