在共液中居住的共巨细胞:在传染性和炎症性关节炎中对免疫调节的影响
Karen I Cyndari1,2, Breanna M Scorza2,3, Zeb R Zacharias4,5
1Department of Emergency Medicine, University of Iowa, Iowa City, IA.
bioRxiv : the preprint server for biology
|October 24, 2023
概括
研究人员在突液中确定了居住突巨细胞 (RSM),揭示了它们的迁移能力和在发病性和炎症性关节炎中起作用. 这些M2扭曲的RSM是关节免疫反应的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 类风湿病学 类风湿病学
背景情况:
- 居住性突巨细胞 (RSM) 对关节免疫常态稳定至关重要.
- 它们在引发和延续关节炎中的作用需要进一步阐明.
- 了解RSM功能是开发针对关节炎的向治疗的关键.
研究的目的:
- 识别和表征在突液 (SF) 中的居住突巨细胞 (RSM).
- 为了证明RSM的迁徙潜力.
- 调查RSM中可能导致慢性关节炎症的功能变化.
主要方法:
- 流细胞测量用于识别周围血液和SF中的单核细胞.
- 使用人类的ex-vivo synovium进行的新型跨井迁移试验.
- 单细胞RNA测序 (scRNA-seq) 用于巨细胞/单细胞子集的识别.
- 测试ELISA以评估SF的骨再吸收潜力.
主要成果:
- 在SF中发现了一种罕见的CD14dim,OPG+,ZO-1+细胞群,与RSM一致.
- 在感染期间,RSM富含SF,但与对照组相比,绝对数量下降.
- 活体迁移测定证实了RSM向MCP-1和LPS的迁移能力.
- scRNA-seq揭示的RSM在转录上与细胞毒性树突细胞和M2巨细胞有关.
结论:
- 在SF中发现了一种罕见的,迁徙的RSM群体,能够启动或协调急性 (败血症) 和慢性 (炎症性) 关节炎.
- RSM是M2歪曲的,具有抗原呈现能力,在和炎症性关节炎中表现出保存的功能.
- 这些发现凸显了RSM作为关节免疫和病理学的关键参与者.
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