AUTHOR=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 TITLE=Single-cell multi-omics reveals the TNF-α activation threshold for Classical Monocytes by studying healthy donors and rheumatoid arthritis patients JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1572823 DOI=10.3389/fimmu.2025.1572823 ISSN=1664-3224 ABSTRACT=IntroductionTumor 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.MethodsIn 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.ResultsWe 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.DiscussionThe 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.