Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier
Source abstract
Abstract
Abstract Type 2 diabetes (T2D) is a risk factor for mucosal homeostasis and enhances the susceptibility to inflammation, in which neutrophils have been increasingly appreciated for their role. 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‐metabolic axis in neutrophil, thereby suggesting a potential therapeutic strategy.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Oral microbiology and periodontitis research · Neutrophil, Myeloperoxidase and Oxidative Mechanisms · Oral and gingival health research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases West China Hospital of Stomatology Sichuan University Chengdu Sichuan 610041 China
Department of Prosthodontics Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu 611731 China
Department of Basic and Translational Sciences Laboratory of Innate Immunity and Inflammation Penn Dental Medicine University of Pennsylvania Philadelphia PA 19104 USA
Hebei Key Laboratory of Stomatology Hebei Clinical Research Center for Oral Diseases Hebei Medical University Shijiazhuang Hebei 050017 China
Division of Preventive and Restorative Sciences School of Dentistry University of California Los Angeles Los Angeles CA 90095 USA
Department of Implantology West China Hospital of Stomatology Sichuan University Chengdu Sichuan 610041 China
Funding
National Natural Science Foundation of China
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