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Here, barrier disruption and inflammation are observed at oral mucosa (gingiva) of T2D patients and mice. It is demonstrated that neutrophils infiltrate the gingival mucosa of T2D mice and expel obvious neutrophil extracellular traps (NETs), while removal of NETs alleviates the disruption of mucosal barrier. Mechanistically, gingival neutrophils released NETs are dependent of their metabolic reprogramming. Under hyperglycemic condition, neutrophils elevate both glucose incorporation and glycolysis via increased expression of GLUT1. Moreover, significantly increased levels of NETs are observed in local gingival lesions of patients, which are associated with clinical disease severity. This work elucidates a causative link between hyperglycemia and oral mucosal immunopathology, mediated by the altered immuno\u2010metabolic axis in neutrophil, thereby suggesting a potential therapeutic strategy.<\/jats:p>","DOI":"10.1002\/advs.202407346","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T13:54:19Z","timestamp":1730814859000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Hyperglycemia\u2010Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier"],"prefix":"10.1002","volume":"11","author":[{"given":"Qian","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University  Chengdu Sichuan 610041 China"},{"name":"Department of Prosthodontics Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu 611731 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; 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