ORIGINAL RESEARCH article

Front. Immunol.

Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1572823

This article is part of the Research TopicMathematical Modeling in Discovery and Analysis of Immune ResponsesView all 6 articles

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

Provisionally accepted
Roman Perik-ZavodskiiRoman Perik-Zavodskii1,2*Olga Perik-ZavodskaiaOlga Perik-Zavodskaia1Saleh AlrhmounSaleh Alrhmoun1,2Julia LopatnikovaJulia Lopatnikova1,2Alina AlshevskayaAlina Alshevskaya2Julia ZhukovaJulia Zhukova1,2Julia ShevchenkoJulia Shevchenko1,2Nadezhda ShkarubaNadezhda Shkaruba3Natalia SivitskayaNatalia Sivitskaya2Shakir SuleimanovShakir Suleimanov2Elizaveta ShevelevaElizaveta Sheveleva2Kirill NazarovKirill Nazarov1Fedor KireevFedor Kireev1,2Alexey SizikovAlexey Sizikov3Elena Alekseevna GolikovaElena Alekseevna Golikova2Sergey Vital'evich SennikovSergey Vital'evich Sennikov1,2
  • 1Research Institute for Fundamental and Clinical Immunology (NIIFKI), Novosibirsk, Russia
  • 2I.M. Sechenov First Moscow State Medical University, Moscow, Moscow Oblast, Russia
  • 3Clinic of Immunopathology, Research Institute for Fundamental and Clinical Immunology (NIIFKI), Novosibirsk, Novosibirsk Oblast, Russia

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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. 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. 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. 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.

Keywords: TNF-α, TNFR1, TNFR2, response to TNF-α, Rheumatoid arthritis, CITE-seq, ScRNA-seq

Received: 07 Feb 2025; Accepted: 29 Apr 2025.

Copyright: © 2025 Perik-Zavodskii, Perik-Zavodskaia, Alrhmoun, Lopatnikova, Alshevskaya, Zhukova, Shevchenko, Shkaruba, Sivitskaya, Suleimanov, Sheveleva, Nazarov, Kireev, Sizikov, Golikova and Sennikov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Roman Perik-Zavodskii, Research Institute for Fundamental and Clinical Immunology (NIIFKI), Novosibirsk, Russia

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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