IL-21/anti-Tim1/CD40 ligand promotes B10 activity in vitro and alleviates bone loss in experimental periodontitis in vivo.
IL-21/anti-Tim1/CD40 ligand promotes B10 activity in vitro and alleviates bone loss in experimental periodontitis in vivo.
复制标题
IL-21/抗TIM1/CD40配体在体外促进B10活性，并减轻体内实验牙周炎的骨质损失。
DOI：
10.1016/j.bbadis.2017.06.001
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Han X
中科院分区：
文献类型：
--
作者：
Hu Y;Yu P;Yu X;Hu X;Kawai T;Han X
表达IL-10的调节性B细胞(B10)通过抑制过度的炎症反应在免疫系统平衡中发挥重要作用。本研究在体外诱导B10细胞的IL-10活性，并观察其对实验性牙周炎的治疗作用。从C57BL/6J小鼠分离脾B细胞，在对照组、CD40L、IL-21、抗Tim1、CD40L+IL-21、CD40L+抗Tim1、CD40L+IL-21+抗Tim1的条件下培养48h。用丝线结扎C57BL/6J小鼠上颌第二磨牙两周。分别于第3、6、9天将CD40L、IL-21、抗Tim1抗体和Vehicle优化组合注入对侧腭部牙周，于第14天采集上颌骨和牙周组织，分别测定IL-10的表达和牙周骨吸收情况。结果表明，CD40L、IL-21和抗TIM1联合作用后，脾B细胞IL-10的表达明显高于对照组。联合注射CD40L、IL-21和抗Tim1后，牙周组织中IL-10mRNA和蛋白的表达较对照侧明显增加。联合治疗侧牙周组织RANKL表达和牙周骨丢失较对照侧明显减少。提示IL-21、抗TIM1和CD40L联合应用可在体外诱导B10细胞的IL-10活性，抑制结扎剂诱导的实验性牙周炎的牙周骨丢失。
IL-10-expressing regulatory B cells (B10) play an essential role in immune system balance by suppressing excessive inflammatory responses. In this study, we investigated induction of B 10 cell’s IL-10 competency in vitro and its effect on ligature-induced experimental periodontitis in vivo. Spleen B cells were isolated from C57BL/6J mice and cultured for 48 h under the following conditions: control, CD40L, IL-21, anti-Tim1, CD40L +IL-21, CD40L +anti-Tim1, CD40L +IL-21 +anti-Tim1. Silk ligatures were tied around both maxillary second molars of C57BL/6J mice for two weeks. Optimized combination of CD40L, IL-21 and anti-Tim1 and vehicle were injected into contralateral side of palatal gingiva on days 3, 6 and 9. The palatal gingival tissues and maxillary bone were collected on day 14 to determine expressions of IL-10 and periodontal bone resorption respectively. Our results demonstrated that IL-10 expressions of cultured spleen B cells were significantly increased in the presence of CD40L, IL-21 and anti-Tim1 combination when compared with control groups. Gingival IL-10 mRNA and protein expressions were significantly increased after injection of CD40L, IL-21 and anti-Tim1 combination, when compared to the control side. The gingival RANKL expression and periodontal bone loss were significantly decreased on the combination treatment side, as compared to the control side. These results suggest that combination of IL-21, anti-Tim1 and CD40L treatment induced B10 cell’s IL-10 competency in vitro and inhibited periodontal bone loss in ligature-induced experimental periodontitis.
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影响因子：
7.3
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