Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier
Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier
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DOI：
10.1126/science.abl5450
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发表时间：
2021-12-24
期刊：
影响因子：
56.9
通讯作者：
Moutsopoulos, Niki M.
中科院分区：
文献类型：
--
作者：
Silva, Lakmali M.;Doyle, Andrew D.;Moutsopoulos, Niki M.
特定于组织的线索对于粘膜屏障的动态平衡至关重要。在这里，我们报告凝血因子纤维蛋白是口腔粘膜屏障中性粒细胞功能的关键调节因子。我们证明，共生微生物区系触发口腔粘膜中血管外纤维蛋白的沉积。纤维蛋白通过α(M)β(2)整合素受体与中性粒细胞结合，激活效应器功能，包括产生活性氧物种和中性粒细胞细胞外陷阱的形成。在小鼠和人类纤溶酶介导的纤溶功能受损的情况下，这些免疫保护性中性粒细胞功能会造成组织损伤。一致地，编码纤溶酶原的PLG基因多态与常见的牙周病有关。因此，纤维蛋白是中性粒细胞效应器功能的关键调节因子，纤维蛋白-中性粒细胞结合可能是一种常见的粘膜疾病的致病诱因。
Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we report that the clotting factor fibrin is a critical regulator of neutrophil function at the oral mucosal barrier. We demonstrate that commensal microbiota trigger extravascular fibrin deposition in the oral mucosa. Fibrin engages neutrophils through the alpha(M)beta(2) integrin receptor and activates effector functions, including the production of reactive oxygen species and neutrophil extracellular trap formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis in mice and humans. Concordantly, genetic polymorphisms in PLG, encoding plasminogen, are associated with common forms of periodontal disease. Thus, fibrin is a critical regulator of neutrophil effector function, and fibrin-neutrophil engagement may be a pathogenic instigator for a prevalent mucosal disease.