Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier
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.
Authors
- Yuyu Li (ORCID: https://orcid.org/0000-0003-3483-4102)
- Shuqin Cao (ORCID: https://orcid.org/0000-0002-1143-8919)
- Bo Yu (ORCID: https://orcid.org/0000-0002-5955-6332)
- Weimin Lin (ORCID: https://orcid.org/0000-0002-8023-213X)
- Shuang Jiang (ORCID: https://orcid.org/0000-0002-1182-0018)
- Quan Yuan (ORCID: https://orcid.org/0000-0002-2836-1081)
- Kexin Lei (ORCID: https://orcid.org/0000-0001-8778-5506)
- Danting Zhang (ORCID: https://orcid.org/0000-0001-7205-8795)
- Xiaohan Zhang (ORCID: https://orcid.org/0000-0003-1531-3061)
- Hui Wang (ORCID: https://orcid.org/0000-0002-0055-7357)
- Qi Yin (ORCID: https://orcid.org/0000-0002-6392-9736)
- Wen Wang (ORCID: https://orcid.org/0000-0002-2350-3562)
- Yuan Wang (ORCID: https://orcid.org/0009-0001-8115-8699)
- Qian Wang (ORCID: https://orcid.org/0000-0002-6052-9665)
Institutions
- Hebei Medical University (CN)
- University of Electronic Science and Technology of China (CN)
- University of California, Los Angeles (US)
- Sichuan University (CN)
- West China Hospital of Sichuan University (CN)
- University of Pennsylvania (US)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-11-05
- DOI
- https://doi.org/10.1002/advs.202407346
- Citations
- 10
- Primary Topic
- Oral microbiology and periodontitis research
- Type
- article
- Field-Weighted Citation Impact
- 4.00
Funders
- National Natural Science Foundation of China
- Sichuan University
- Army Medical University