单细胞多组学通过研究健康供体和类风湿性关节炎患者揭示了经典单核细胞的TNF-α激活阈值。
Single-cell multi-omics reveals the TNF-α activation threshold for Classical Monocytes by studying healthy donors and rheumatoid arthritis patients.
作者信息
Perik-Zavodskii Roman, Perik-Zavodskaia Olga, Alrhmoun Saleh, Lopatnikova Julia, Alshevskaya Alina, Zhukova Julia, Shevchenko Julia, Shkaruba Nadezhda, Sivitskaya Natalia, Suleimanov Shakir, Sheveleva Elizaveta, Nazarov Kirill, Kireev Fedor, Sizikov Alexey, Golikova Elena, Sennikov Sergey
机构信息
Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.
Laboratory of Immune Engineering, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.
出版信息
Front Immunol. 2025 May 16;16:1572823. doi: 10.3389/fimmu.2025.1572823. eCollection 2025.
INTRODUCTION
Tumor Necrosis Factor Alpha is a known pro-inflammatory cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Anti-cytokine therapies targeting Tumor Necrosis Factor Alpha have greatly succeeded in treating rheumatoid arthritis in many patients. Despite these developments, many of the mechanisms of Tumor Necrosis Factor Alpha action have yet to be uncovered.
METHODS
In this study, we incubated PBMCs from healthy donors and rheumatoid arthritis patients with Tumor Necrosis Factor Alpha and then performed their single-cell multi-omics analysis via BD Rhapsody.
RESULTS
We have observed that Classical Monocytes have responded to the Tumor Necrosis Factor Alpha stimulation the most and that there was an activational threshold for such response that was dependent on the TNFR2 protein expression level.
DISCUSSION
The profiling of TNFR2 protein expression level on immune cell populations can be a good predictive factor for the assessment of their activation by Tumor Necrosis Factor Alpha.
引言
肿瘤坏死因子α是一种已知的促炎细胞因子，在类风湿性关节炎的发病机制中起关键作用。针对肿瘤坏死因子α的抗细胞因子疗法在许多患者的类风湿性关节炎治疗中取得了巨大成功。尽管有这些进展，但肿瘤坏死因子α作用的许多机制尚未被揭示。
方法
在本研究中，我们将来自健康供体和类风湿性关节炎患者的外周血单核细胞与肿瘤坏死因子α一起孵育，然后通过BD Rhapsody对其进行单细胞多组学分析。
结果
我们观察到经典单核细胞对肿瘤坏死因子α刺激的反应最为明显，并且这种反应存在一个激活阈值，该阈值取决于TNFR2蛋白表达水平。
讨论
免疫细胞群体上TNFR2蛋白表达水平的分析可以作为评估其被肿瘤坏死因子α激活的良好预测因子。
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