Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection
Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection
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DOI：
10.1172/jci10763
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发表时间：
2000-09-01
影响因子：
15.9
通讯作者：
Penninger, JM
中科院分区：
文献类型：
--
作者：
Teng, YTA;Nguyen, H;Penninger, JM
牙周炎是人类牙齿脱落的主要原因，与全身性疾病如心力衰竭、中风和细菌性肺炎的风险增加有关。牙周炎和抗菌免疫导致牙槽骨和牙齿脱落的机制知之甚少。为了研究人类对特定牙周感染的免疫应答，黑麦将牙周炎患者的人外周血淋巴细胞（HuPBL）移植到NOD/SCID小鼠体内。HuPBL-NOD/SCID小鼠口服放线菌共生放线杆菌（一种引起人类牙周炎的已知革兰氏阴性厌氧微生物），激活牙周组织中的人类CD 4（+）T细胞并引发局部牙槽骨破坏。人CD 4（+）T细胞，而不是CD 8（+）T细胞或B细胞，被确定为牙槽骨破坏的重要介质。用A.伴随放线菌诱导产生骨保护素配体（OPG-L），其是破骨细胞生成和破骨细胞活化的关键调节剂。在体内用诱饵受体OPG抑制OPG-L功能可减少牙槽骨破坏，并减少微生物挑战后牙周膜破骨细胞的数量。这些数据表明，牙周感染中观察到的牙槽骨破坏的分子解释是由微生物触发的CD 4（+）T细胞上OPG-L表达的诱导和破骨细胞的随后激活介导的。因此，抑制OPG-L可能对预防人类牙周炎中的牙槽骨和/或牙齿脱落具有治疗价值。
Periodontitis, a prime cause of tooth loss in humans, is implicated in the increased risk of systemic diseases such as heart failure, stroke, and bacterial pneumonia. The mechanisms by which periodontitis and antibacterial immunity lead to alveolar bone and tooth loss are poorly understood. To study the human immune response to specific periodontal infections, rye transplanted human peripheral blood lymphocytes (HuPBLs) from periodontitis patients into NOD/SCID mice. Oral challenge of HuPBL-NOD/SCID mice with Actinobacillus actinomycetemcomitans, a well-known Gram-negative anaerobic microorganism that causes human periodontitis, activates human CD4(+) T cells in the periodontium and triggers local alveolar bone destruction. Human CD4(+) T cells, but not CD8(+) T cells or B cells, are identified as essential mediators of alveolar bone destruction. Stimulation of CD4(+) T cells by A. actinomycetemcomitans induces production of osteoprotegerin ligand (OPG-L), a key modulator of osteoclastogenesis and osteoclast activation. In vivo inhibition of OPG-L function with the decoy receptor OPG diminishes alveolar bone destruction and reduces the number of peridontal osteoclasts after microbial challenge. These data imply that the molecular explanation for alveolar bone destruction observed in perio dental infections is mediated by microorganism-triggered induction of OPG-L expression on CD4(+) T cells and the consequent activation of osteoclasts. Inhibition of OPG-L may thus have therapeutic value to prevent alveolar bone and/or tooth loss in human periodontitis.