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维甲酸激动剂Am80通过调节Treg/Th17平衡改善牙周炎

Retinoid Agonist Am80 Ameliorates Bone Destruction through the Modulation of Treg/Th17 Cells

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【作者】 靳赢王琳源林晓萍吕昌龙王金岩

【Author】 JIN Ying;WANG Linyuan;LIN Xiaoping;LV Changlong;WANG Jinyan;Department of Immunology, College of Basic Medical Sciences, China Medical University;Department of Stomatology, Shengjing Hospital of China Medical University;

【机构】 中国医科大学基础医学院免疫学教研室中国医科大学附属盛京医院口腔科

【摘要】 Treg细胞和Th17细胞及其分泌的细胞因子在牙周炎病理形成中起着重要的作用。全反式维甲酸抑制Th17细胞的活化并促进Treg细胞转录因子Foxp3的表达阻止实验性牙周炎的病理进程。本研究通过组织化学染色、流式细胞仪及Realtime PCR等方法,发现Am80显著抑制P.gingivalis W83诱导的牙周骨吸收,减轻牙周组织炎症。这种作用与降低牙周组织中CD4+ROR-γt+细胞的数量,增加CD4+Foxp3+细胞的数量有关。进一步研究发现,AM80显著下调牙周炎小鼠牙周组织和局部淋巴结中IL-17A、RANKL、MCP-1、IL-6、IL-1βmRNA的表达水平,上调Treg细胞相关因子IL-10和TGF-β1的mRNA的表达水平。研究结果表明,Am80通过活化Treg细胞以及抑制Th17细胞,调节Treg/Th17细胞的平衡等机制改善牙实验性周炎症。

【Abstract】 Association between periodontal diseases with Treg/Th17 cells has long been recognized. As previous studies shown, all-trans retinoic acid has been suggested to inhibit Th17 polarization and enhance FOXP3 expression in inflammatory diseases. The current study investigated a role of Am80 in regulation of Treg/Th17 cell imbalance and effects on periodontal disease. Our data showed that Am80 suppressed alveolar bone resorption, inhibited the infiltration of inflammatory cells, and decreased the number of osteocleast in periodontal tissues. These effects were closely associated with reduced frequency of CD4+RORγt+ cells and increased frequency of CD4+Foxp3+ cells in the CLNs. Furthermore, Am80 down-regulated IL-17A, RANKL, MCP-1, IL-6, IL-1β mRNA expression and up-regulated IL-10 and TGF-β1 expression in both the CLNs and P. gingivalis-infected gingival tissues. The results suggest that Am80 regulates Th17/Treg imbalance by enhancing the activation of Treg cells and inhibiting Th17 cell activation, thus providing protection against periodontitis. These results indicate the potential of AM80 for the clinical therapy of periodontitis.

  • 【会议录名称】 第十六届中国科协年会——分13感染、免疫和疫苗论坛论文集
  • 【会议名称】第十六届中国科协年会——分13感染、免疫和疫苗论坛
  • 【会议时间】2014-05-24
  • 【会议地点】中国云南昆明
  • 【分类号】R781.4
  • 【主办单位】中国科学技术协会、云南省人民政府
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