Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier
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. I...
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| Format: | Article |
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407346 |
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| author | Qian Wang Weimin Lin Kexin Lei Hui Wang Xiaohan Zhang Shuang Jiang Danting Zhang Wen Wang Shuqin Cao Yuyu Li Bo Yu Yuan Wang Qi Yin Quan Yuan |
| author_facet | Qian Wang Weimin Lin Kexin Lei Hui Wang Xiaohan Zhang Shuang Jiang Danting Zhang Wen Wang Shuqin Cao Yuyu Li Bo Yu Yuan Wang Qi Yin Quan Yuan |
| author_sort | Qian Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bacd29c1edb14d2e92f59a0e344456fb |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-bacd29c1edb14d2e92f59a0e344456fb2025-08-20T02:52:41ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202407346Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral BarrierQian Wang0Weimin Lin1Kexin Lei2Hui Wang3Xiaohan Zhang4Shuang Jiang5Danting Zhang6Wen Wang7Shuqin Cao8Yuyu Li9Bo Yu10Yuan Wang11Qi Yin12Quan Yuan13State 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 ChinaState 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 ChinaState 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 ChinaDepartment of Basic and Translational Sciences Laboratory of Innate Immunity and Inflammation Penn Dental Medicine University of Pennsylvania Philadelphia PA 19104 USAState 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 ChinaState 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 ChinaState 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 ChinaHebei Key Laboratory of Stomatology Hebei Clinical Research Center for Oral Diseases Hebei Medical University Shijiazhuang Hebei 050017 ChinaState 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 ChinaState 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 ChinaDivision of Preventive and Restorative Sciences School of Dentistry University of California Los Angeles Los Angeles CA 90095 USAState 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 ChinaState 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 ChinaState 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 ChinaAbstract 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.https://doi.org/10.1002/advs.202407346glucose transporter 1glycolysishyperglycemianeutrophilsoral mucosal immunitytype 2 diabetes |
| spellingShingle | Qian Wang Weimin Lin Kexin Lei Hui Wang Xiaohan Zhang Shuang Jiang Danting Zhang Wen Wang Shuqin Cao Yuyu Li Bo Yu Yuan Wang Qi Yin Quan Yuan Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier Advanced Science glucose transporter 1 glycolysis hyperglycemia neutrophils oral mucosal immunity type 2 diabetes |
| title | Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier |
| title_full | Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier |
| title_fullStr | Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier |
| title_full_unstemmed | Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier |
| title_short | Hyperglycemia‐Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier |
| title_sort | hyperglycemia enhanced neutrophil extracellular traps drive mucosal immunopathology at the oral barrier |
| topic | glucose transporter 1 glycolysis hyperglycemia neutrophils oral mucosal immunity type 2 diabetes |
| url | https://doi.org/10.1002/advs.202407346 |
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