In knee osteoarthritis, the production of cytokines and metalloproteinases in presence of chondrocytes and CD4+ T cells depends on T cell subset: An in vitro analysis

IF 2.8
H. Platzer , M. Wellbrock , G. Pourbozorg , R. Mayakrishnan , S. Gantz , B. Khamees , S. Maciej , B. Moradi
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引用次数: 0

Abstract

Objective

Osteoarthritis (OA) is driven by biomechanical and biochemical inflammatory processes, including CD4+ T cell infiltration and activation. However, the role of CD4+ T cell subsets interacting with neighboring cells shaping the local inflammatory milieu have remained largely unexplored. This study aimed to investigate in vitro whether interaction of chondrocyte and CD4+ T cells modulate cytokine and metalloproteinase production in OA, and to determine if this modulation differ depending on CD4+ T cell subsets.

Method

Nineteen patients with knee OA undergoing knee replacement were enrolled. From peripheral blood CD4+ T cells were isolated and differentiated into subsets (Th1, Th2, Th17, Treg) using a novel developed protocol. T cell differentiation was validated by flow cytometry. Chondrocytes were mono- and co-cultured with T cell subsets and in culture supernatant cytokine and metalloproteinase levels were quantified using ELISA and multiplex assays.

Results

Compared to monocultures levels MMP-1/3/9/13 and IL-6 were elevated in all co-cultures of chondrocytes and CD4+ T cell subsets, with the highest levels in Th17 co-cultures. GM-CSF, IL-9, IL-17 were specifically elevated in Th17 co-cultures and IFN-γ in Th1 co-cultures. TNF-α production was significantly reduced only in Treg co-culture compared to monoculture approach.

Conclusion

This study indicates that chondrocytes can interact with CD4+ T cell subsets in OA, modulating the production of metalloproteinases and cytokines to varying degrees, depending on the CD4+ T cell subset. Our findings can open new avenues in OA treatment using T cell-based or T cell subset-targeted therapies to modulate inflammatory patterns in affected OA joints.
在膝关节骨关节炎中,存在软骨细胞和CD4+ T细胞的细胞因子和金属蛋白酶的产生取决于T细胞亚群:一项体外分析
目的骨关节炎(OA)是由生物力学和生化炎症过程驱动的,包括CD4+ T细胞的浸润和活化。然而,CD4+ T细胞亚群与邻近细胞相互作用形成局部炎症环境的作用在很大程度上仍未被探索。本研究旨在体外研究软骨细胞和CD4+ T细胞的相互作用是否调节OA中细胞因子和金属蛋白酶的产生,并确定这种调节是否取决于CD4+ T细胞亚群。方法19例膝关节OA患者行膝关节置换术。从外周血中分离CD4+ T细胞并使用新开发的方案将其分化为亚群(Th1, Th2, Th17, Treg)。流式细胞术证实T细胞分化。软骨细胞与T细胞亚群单独或共培养,用ELISA和多重检测法定量培养上清细胞因子和金属蛋白酶水平。结果与单培养相比,MMP-1/3/9/13和IL-6在所有软骨细胞和CD4+ T细胞亚群共培养中均升高,其中Th17共培养水平最高。Th17共培养中GM-CSF、IL-9、IL-17特异性升高,Th1共培养中IFN-γ特异性升高。与单一培养相比,只有Treg共培养显著降低了TNF-α的产生。结论软骨细胞在骨性关节炎中可与CD4+ T细胞亚群相互作用,不同程度地调节金属蛋白酶和细胞因子的产生,这取决于CD4+ T细胞亚群。我们的研究结果可以为使用基于T细胞或T细胞亚群靶向治疗来调节受影响OA关节的炎症模式开辟新的途径。
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来源期刊
Osteoarthritis and cartilage open
Osteoarthritis and cartilage open Orthopedics, Sports Medicine and Rehabilitation
CiteScore
3.30
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0.00%
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