Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms
<b><b>Introduction:</b></b> Immunosenescence alters TNF receptor expression (TNFR1 and TNFR2), contributing to chronic inflammation (inflamm-aging) and age-related diseases. Polymorphisms in TNFRSF1A and TNFRSF1B may influence receptor expression; however, their role in age-d...
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2025-04-01
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| author | Alina Alshevskaya Julia Zhukova Julia Lopatnikova Filipp Vasilyev Ivan Khutornoy Elena Golikova Fedor Kireev Sergey Sennikov |
| author_facet | Alina Alshevskaya Julia Zhukova Julia Lopatnikova Filipp Vasilyev Ivan Khutornoy Elena Golikova Fedor Kireev Sergey Sennikov |
| author_sort | Alina Alshevskaya |
| collection | DOAJ |
| description | <b><b>Introduction:</b></b> Immunosenescence alters TNF receptor expression (TNFR1 and TNFR2), contributing to chronic inflammation (inflamm-aging) and age-related diseases. Polymorphisms in TNFRSF1A and TNFRSF1B may influence receptor expression; however, their role in age-dependent modulation remains unclear. This study examines TNFR1/TNFR2 expression dynamics on T cells, B cells, and monocytes across different ages and evaluates the impact of genetic polymorphisms. <b>Methods:</b> PBMCs from 150 donors (18–60 years) were isolated via density-gradient centrifugation and cultured under spontaneous and LPS-stimulated conditions. TNFR1 and TNFR2 expression on immune cell subsets was quantified using flow cytometry with BD QuantiBRITE PE beads. SNP genotyping in TNFRSF1A and TNFRSF1B was performed via PCR with restriction analysis. Nonlinear age-related trends were assessed using polynomial approximation and inflection point analysis (Tukey’s method). <b>Results:</b> Among the 23 analyzed TNF system parameters, the proportion of TNFR2<sup>+</sup>CD3<sup>+</sup> T cells increased with age, whereas TNFR1<sup>+</sup> and TNFR2<sup>+</sup> monocyte populations showed significant negative correlations (<i>p</i> < 0.05). Inflection points (~27, 34–36, and 44–45 years) indicated nonlinear dynamics in TNFRs expression during aging. TNFR2 expression on T cells gradually increased and stabilized at later ages, whereas TNFR1 and TNFR2 expression on monocytes followed distinct declining trajectories. Genetic polymorphisms influenced correlation strength, but did not alter direction, demonstrating a conserved pattern of age-related receptor expression shifts. <b>Conclusions:</b> TNFR expression exhibits nonlinear, age-dependent alterations across immune cells, shaped by immunosenescence and genetic variability. The identified critical age intervals represent key phases of immune remodeling, where assessing TNFR expression may provide insights into inflamm-aging mechanisms and potential targets for immune modulation. |
| format | Article |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-576bb9bfa5f84f5092215546db654c442025-08-20T02:17:20ZengMDPI AGBiomedicines2227-90592025-04-0113485210.3390/biomedicines13040852Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging MechanismsAlina Alshevskaya0Julia Zhukova1Julia Lopatnikova2Filipp Vasilyev3Ivan Khutornoy4Elena Golikova5Fedor Kireev6Sergey Sennikov7Federal 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 119048, RussiaFederal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaFederal 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 119048, RussiaFederal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLomonosov Moscow State University, Moscow 119991, RussiaFederal 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 119048, RussiaFederal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaFederal 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 119048, Russia<b><b>Introduction:</b></b> Immunosenescence alters TNF receptor expression (TNFR1 and TNFR2), contributing to chronic inflammation (inflamm-aging) and age-related diseases. Polymorphisms in TNFRSF1A and TNFRSF1B may influence receptor expression; however, their role in age-dependent modulation remains unclear. This study examines TNFR1/TNFR2 expression dynamics on T cells, B cells, and monocytes across different ages and evaluates the impact of genetic polymorphisms. <b>Methods:</b> PBMCs from 150 donors (18–60 years) were isolated via density-gradient centrifugation and cultured under spontaneous and LPS-stimulated conditions. TNFR1 and TNFR2 expression on immune cell subsets was quantified using flow cytometry with BD QuantiBRITE PE beads. SNP genotyping in TNFRSF1A and TNFRSF1B was performed via PCR with restriction analysis. Nonlinear age-related trends were assessed using polynomial approximation and inflection point analysis (Tukey’s method). <b>Results:</b> Among the 23 analyzed TNF system parameters, the proportion of TNFR2<sup>+</sup>CD3<sup>+</sup> T cells increased with age, whereas TNFR1<sup>+</sup> and TNFR2<sup>+</sup> monocyte populations showed significant negative correlations (<i>p</i> < 0.05). Inflection points (~27, 34–36, and 44–45 years) indicated nonlinear dynamics in TNFRs expression during aging. TNFR2 expression on T cells gradually increased and stabilized at later ages, whereas TNFR1 and TNFR2 expression on monocytes followed distinct declining trajectories. Genetic polymorphisms influenced correlation strength, but did not alter direction, demonstrating a conserved pattern of age-related receptor expression shifts. <b>Conclusions:</b> TNFR expression exhibits nonlinear, age-dependent alterations across immune cells, shaped by immunosenescence and genetic variability. The identified critical age intervals represent key phases of immune remodeling, where assessing TNFR expression may provide insights into inflamm-aging mechanisms and potential targets for immune modulation.https://www.mdpi.com/2227-9059/13/4/852TNFR1TNFR2age-related receptor expressionimmune cell subsetsTNF signalinggenetic polymorphisms |
| spellingShingle | Alina Alshevskaya Julia Zhukova Julia Lopatnikova Filipp Vasilyev Ivan Khutornoy Elena Golikova Fedor Kireev Sergey Sennikov Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms Biomedicines TNFR1 TNFR2 age-related receptor expression immune cell subsets TNF signaling genetic polymorphisms |
| title | Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms |
| title_full | Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms |
| title_fullStr | Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms |
| title_full_unstemmed | Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms |
| title_short | Nonlinear Dynamics of TNFR1 and TNFR2 Expression on Immune Cells: Genetic and Age-Related Aspects of Inflamm-Aging Mechanisms |
| title_sort | nonlinear dynamics of tnfr1 and tnfr2 expression on immune cells genetic and age related aspects of inflamm aging mechanisms |
| topic | TNFR1 TNFR2 age-related receptor expression immune cell subsets TNF signaling genetic polymorphisms |
| url | https://www.mdpi.com/2227-9059/13/4/852 |
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