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治疗性CCL2调节免疫反应,并恢复宿主微生物平衡
Mostafa Shehabeldin1,2,3, Jin Gao1, Yejin Cho3
1Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
概括
局部输送的骨髓细胞招募化学基因CCL2有效地治疗小鼠的牙周病. 这种疗法可以减少骨质损失,促进骨质增益,并通过调节免疫反应来恢复微生物平衡.
科学领域:
- 免疫学和微生物学
- 口腔生物学 口腔生物学
- 再生医学是一种再生医学.
背景情况:
- 慢性炎症性疾病往往源于不受调节的宿主-微生物相互作用.
- 牙周病 (PD) 是一种常见的疾病,涉及微生物失生症,导致炎症,骨质损失和牙损失.
研究的目的:
- 在牙周病的小鼠模型中,研究骨髓细胞招募化学激素 (C-C动机) 连接体2 (CCL2) 的局部持续输送的治疗潜力.
- 评估CCL2作为PD的预防性,干预性或修复性疗法的效果.
主要方法:
- 采用了一种小鼠结带诱导的牙周病模型.
- 管理的局部持续交付CCL2.2.
- 进行了微计算断层扫描用于骨分析,流细胞测量用于免疫细胞分析,单细胞RNA测序用于转录组分析,以及16SrRNA测序用于微生物评估.
主要成果:
- 局部CCL2输送显著抑制了骨损失,并通过减少骨质细胞数量加速了骨的增加.
- CCL2治疗调节了巨细胞群 (上调的M2,下调的亲炎症/亲骨质细胞标志物) 和逆转了与疾病相关的转录组形状.
- 治疗减轻了微生物失调,减少了微生物负载,与改善的骨参数相关.
结论:
- 局部持续的CCL2输送在实验性牙周病中显示出显著的治疗益处.
- CCL2疗法提供了一种新的方法来管理由宿主微生物失衡驱动的慢性炎症疾病.
- 该战略强调了针对免疫细胞招募用于组织再生和疾病控制的潜力.
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