损伤和肥胖差异和协同诱导骨关节炎滑膜免疫细胞失调。

IF 20.3 1区 医学 Q1 RHEUMATOLOGY
Annals of the Rheumatic Diseases Pub Date : 2025-06-01 Epub Date: 2025-04-04 DOI:10.1016/j.ard.2025.03.001
Natalia S Harasymowicz, Zainab Harissa, Neda Rashidi, Kristin Lenz, Ruhang Tang, Farshid Guilak
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引用次数: 0

摘要

目的:免疫细胞的异质性和表型协调了许多生理和病理过程。最近的证据表明,免疫细胞在骨关节炎(OA)的进展中起关键作用。我们假设损伤和肥胖是OA的两个主要危险因素,它们会影响关节中免疫细胞的主要储存库——滑膜的免疫表型。方法:利用单细胞转录组学、免疫图谱、转基因小鼠模型和遗传命运定位方法,我们表征了在膝关节囊中发现的多个免疫细胞群的存在和命运。结果:我们发现关节损伤和肥胖不同且协同地改变了滑膜囊的结构、细胞和分子特征。我们观察到肥胖动物中巡逻单核细胞较少,并且发现在关节损伤后的前3天,肥胖动物中促炎单核细胞来源的巨噬细胞的流入明显高于对照组。我们还发现,在内侧半月板手术失稳后3天,形成屏障的滑膜衬里巨噬细胞显著减少,正常体重小鼠的巨噬细胞数量显著恢复,但在OA晚期的肥胖小鼠中没有。最后,我们描述了其他免疫细胞亚型的存在和变化,包括T、B、肥大细胞和中性粒细胞,以及与损伤和肥胖相关的局部滑膜液细胞因子。结论:我们的数据显示,损伤和肥胖独立和协同地促进滑膜免疫景观的失调,为它们在OA发病机制中的作用提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Injury and obesity differentially and synergistically induce dysregulation of synovial immune cells in osteoarthritis.

Objectives: The heterogeneity and phenotype of immune cells orchestrate many physiologic and pathologic processes. Recent evidence suggests that immune cells play critical roles in the progression of osteoarthritis (OA). We hypothesised that injury and obesity, two major risk factors for OA, affect the immunophenotype of the synovium, the primary reservoir of immune cells in the joint.

Methods: Using single-cell transcriptomics, immunoprofiling, transgenic mouse models, and genetic fate mapping methods, we characterised the presence and fate of multiple populations of immune cells found in the knee joint capsule.

Results: We found that joint injury and obesity differentially and synergistically alter the architectural, cellular, and molecular profiles of the synovial capsule. We observed fewer patrolling monocytes in obese animals and found a significantly higher influx of proinflammatory monocyte-derived macrophages in the first 3 days after joint injury in obese compared with that in control animals. We also showed a significant loss of barrier-forming synovial lining macrophages 3 days after destabilisation of medial meniscus surgery, with a significant restoration of their numbers in normal weight but not in obese mice in advanced stages of OA. Finally, we characterised the presence and changes of other immune cell subtypes, including T, B, and mast cells and neutrophils, as well as local synovial fluid cytokines associated with injury and obesity.

Conclusions: Our data revealed that injury and obesity independently and synergistically contribute to the dysregulation of the synovial immune landscape, providing new insight into their role in the pathogenesis of OA.

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来源期刊
Annals of the Rheumatic Diseases
Annals of the Rheumatic Diseases 医学-风湿病学
CiteScore
35.00
自引率
9.90%
发文量
3728
审稿时长
1.4 months
期刊介绍: Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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