显著的纤维细胞子集导致关节炎的炎症和损伤
Adam P Croft1,2, Joana Campos1, Kathrin Jansen3
1Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.
Nature
|May 31, 2019
概括
研究人员在关节炎中发现了不同的纤维细胞子集, 针对这些特定的纤维细胞群可能导致免疫介导炎症疾病的新疗法.
科学领域:
- 免疫学
- 细胞生物学
- 关节病学
背景情况:
- 具有独特功能的淋巴细胞子集是针对免疫媒介炎症疾病 (IMID) 的关键治疗方法.
- 功能上不同的纤维细胞子类在IMID中的存在和作用基本上是未知的.
- 纤维细胞参与各种组织过程,包括炎症和损伤,但它们的异质性不明.
研究的目的:
- 识别和描述在关节炎中负责介导炎症或组织损伤的不同纤维细胞子集.
- 在临床前关节炎模型中研究这些纤维细胞子集的功能作用.
- 探索针对IMID特定纤维细胞群的治疗潜力.
主要方法:
- 单细胞转录分析以确定FAPα+群体中的纤维细胞子集.
- 将已识别的纤维细胞子集转移到小鼠关节中以评估它们的功能.
- 使用小鼠解决和持久性关节炎模型来评估纤维细胞子集删除的影响.
主要成果:
- 在FAPα+群体中发现了两个不同的纤维细胞子集:FAPα+THY1+免疫效应纤维细胞和FAPα+THY1-破坏性纤维细胞.
- 在采用转移时,FAPα+THY1-纤维细胞选择性介导骨和软骨损伤.
- FAPα+THY1+纤维细胞诱导更严重和持久的炎症性关节炎,组织损伤最小.
- 在关节炎模型中,删除FAPα+纤维细胞抑制了炎症和骨质侵蚀.
结论:
- 在关节炎中,不同的,在解剖学上定位的纤维细胞子集调解非重叠的功能,导致炎症或组织损伤.
- 这些发现突显了针对性细胞疗法在IMID中调节炎症和组织损伤的潜力.
- 了解纤维细胞异质性对于开发有效的免疫媒介炎症疾病至关重要.
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