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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.


DOI:10.3389/fimmu.2025.1572823
PMID:40453083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12122427/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/587969f0671e/fimmu-16-1572823-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/ba471a8948fe/fimmu-16-1572823-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/18f47bfcdc08/fimmu-16-1572823-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/07089d8d56db/fimmu-16-1572823-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/587969f0671e/fimmu-16-1572823-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/ba471a8948fe/fimmu-16-1572823-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/18f47bfcdc08/fimmu-16-1572823-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/07089d8d56db/fimmu-16-1572823-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1069/12122427/587969f0671e/fimmu-16-1572823-g004.jpg

相似文献

[1]
Single-cell multi-omics reveals the TNF-α activation threshold for Classical Monocytes by studying healthy donors and rheumatoid arthritis patients.

Front Immunol. 2025-5-16

[2]
TNF- Autocrine Feedback Loops in Human Monocytes: The Pro- and Anti-Inflammatory Roles of the TNF- Receptors Support the Concept of Selective TNFR1 Blockade .

J Immunol Res. 2016

[3]
Interaction between transmembrane TNF and TNFR1/2 mediates the activation of monocytes by contact with T cells.

J Immunol. 2007-9-15

[4]
TNFR1 and TNFR2 differentially mediate TNF-α-induced inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes.

Cell Biol Int. 2017-4

[5]
Candidate Markers for Stratification and Classification in Rheumatoid Arthritis.

Front Immunol. 2019-7-5

[6]
Cytokine stimulation of T lymphocytes regulates their capacity to induce monocyte production of tumor necrosis factor-alpha, but not interleukin-10: possible relevance to pathophysiology of rheumatoid arthritis.

Eur J Immunol. 1997-3

[7]
Induction of tumour necrosis factor receptor-expressing macrophages by interleukin-10 and macrophage colony-stimulating factor in rheumatoid arthritis.

Arthritis Res Ther. 2006

[8]
TNF-α Affects Signature Cytokines of Th1 and Th17 T Cell Subsets through Differential Actions on TNFR1 and TNFR2.

Int J Mol Sci. 2022-8-18

[9]
CD56+ monocytes have a dysregulated cytokine response to lipopolysaccharide and accumulate in rheumatoid arthritis and immunosenescence.

Arthritis Res Ther. 2013-10-1

[10]
Inhibition of antigen-presenting cell function and stimulation of human peripheral blood mononuclear cells to express an antiinflammatory cytokine profile by the stress protein BiP: relevance to the treatment of inflammatory arthritis.

Arthritis Rheum. 2004-4

本文引用的文献

[1]
Targeting Precision in Cancer Immunotherapy: Naturally-Occurring Antigen-Specific TCR Discovery with Single-Cell Sequencing.

Cancers (Basel). 2024-11-30

[2]
Decoding NY-ESO-1 TCR T cells: transcriptomic insights reveal dual mechanisms of tumor targeting in a melanoma murine xenograft model.

Front Immunol. 2024-11-26

[3]
Modified Dendritic cell-based T-cell expansion protocol and single-cell multi-omics allow for the selection of the most expanded and -effective clonotype via profiling of thousands of MAGE-A3-specific T-cells.

Front Immunol. 2024

[4]
Single-cell multi-omics reveal stage of differentiation and trajectory-dependent immunity-related gene expression patterns in human erythroid cells.

Front Immunol. 2024

[5]
Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.

Nat Commun. 2024-6-11

[6]
Dendritic cells and antigen-specific immunotherapy in autoimmune rheumatic diseases.

Best Pract Res Clin Rheumatol. 2024-5

[7]
Epidemiology and Risk Factors for Rheumatoid Arthritis Development.

Mediterr J Rheumatol. 2023-12-30

[8]
Role of Inflammatory Cytokines in Rheumatoid Arthritis and Development of Atherosclerosis: A Review.

Medicina (Kaunas). 2023-8-26

[9]
PyDESeq2: a python package for bulk RNA-seq differential expression analysis.

Bioinformatics. 2023-9-2

[10]
The role of dendritic cells and their immunometabolism in rheumatoid arthritis.

Front Immunol. 2023

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