编程死亡干1-表达巨细胞及其在关节炎期间在关节中的保护作用
Megan Kay Wood1, Abdel Daoud1,2, Monica Vladut Talor2
1Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland.
Arthritis & rheumatology (Hoboken, N.J.)
|November 24, 2023
概括
编程死亡连接体1 (PD-L1) 表达巨细胞保护关节免受严重关节炎. 阻止PD-L1会使关节炎恶化,这表明它在维持关节平衡和减少炎症方面发挥着至关重要的作用.
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:
- 免疫检查点抑制剂 (ICI) 可以诱导关节炎,这强调了免疫检查点在关节平衡中的作用.
- 编程死亡连接体1 (PD-L1) 是一个关键的免疫检查点分子.
- 在关节炎期间,其在突组织中的功能尚未完全理解.
研究的目的:
- 通过使用原诱导性关节炎 (CIA) 鼠标模型,研究PD-L1在关节炎期间在关节膜中的作用.
- 确定关节中PD-L1表达细胞的细胞来源和功能.
主要方法:
- 在CIA小鼠模型中用抗体阻止PD-L1.
- 通过临床和组织学评分来评估关节炎的严重程度.
- 通过流式细胞计和对生物体的研究,研究PD-L1表达和巨的起源.
- 使用Cre-Lox小鼠评估PD-L1表达性巨细胞的作用.
- 通过RT-PCR,流细胞测量和单细胞RNA测序来分析人类和小鼠结膜巨细胞的免疫特征.
主要成果:
- 在CIA小鼠中,抗PD-L1治疗加剧了关节炎的严重程度和免疫细胞透.
- 巨被确定为突中主要的PD-L1表达细胞.
- PD-L1+巨细胞表现出增加的MerTK和IL-10表达,并且在本地繁殖和循环.
- 在巨细胞上PD-L1的遗传枯竭使CIA恶化.
- 人类的突PD-L1+巨细胞在恒温和类风湿性关节炎中表达MerTK和IL-10.
结论:
- PD-L1+巨细胞具有细胞和抗炎性质,可以保护突细胞免受严重关节炎的影响.
- 这些组织保护性巨细胞存在于人体突体中,无论是在恒常状态下还是在类风湿性关节炎期间.
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