细胞外微RNA诱导树突细胞依赖的关节炎症,并通过TLR7/8参与来增强骨质细胞分化
Carolina Gaudenzi1, Tiziana Schioppa2, Mauro Passari1
1Department of Molecular and Translational Medicine, University of Brescia, Italy.
Journal of autoimmunity
|March 5, 2024
概括
类风湿性关节炎 (RA) 中的细胞外微RNA通过TLR8激活树突细胞 (DCs),导致炎症和骨破坏. 向TLR8可能是一种新的RA疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 分子生物学分子生物学
背景情况:
- 单细胞衍生的树突细胞 (DCs) 参与了类风湿性关节炎 (RA) 的发病.
- 在RA中DC激活的机制尚不清楚.
- 在RA突发性关节液中的细胞外微RNAs (Ex-miRNAs) 可能会激活DCs.
研究的目的:
- 调查RA突发性关节液中的Ex-miRNA是否会激活DCs.
- 确定TLR8在Ex-miRNA诱导的DC激活中的作用.
- 评估Ex-miRNA激活的DCs对炎症和骨破坏的影响.
主要方法:
- 人类单细胞衍生的DCs被RAEx-miRNAs刺激.
- 评估了DC激活 (NF-κB,细胞因子),T细胞反应和骨质细胞分化.
- 在小鼠关节炎模型中评估关节炎症.
- 使用TLR7/8抑制剂来评估途径的参与.
主要成果:
- 前-miRNAs激活了DCs,导致TNFα分泌.
- 在体内,ex-miRNAs诱导关节炎症和自身免疫反应.
- 由Ex-miRNAs刺激的DCs促进了骨质细胞分化和活性.
- 确定TLR8是调解这些效应的关键受体.
结论:
- 在RA关节中的细胞外微RNA通过TLR8.8激活人类的DC.
- 激活的DCs促进炎症和骨质细胞介导的骨损伤.
- 抑制TLR8是一种潜在的RA治疗策略.
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