Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Sennikov, Sergey; Alshevskaya, Alina; Zhukova, Julia; Belomestnova, Irina; Karaulov, Alexander; Lopatnikova, Julia

doi:10.1159/000494387

Cited by 15 publications

(12 citation statements)

References 70 publications

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“…It is noteworthy that the pathological processes occurring in the body can alter the expression levels of different receptor types, which may be one of the mechanisms explaining why immunocompetent cells exhibit different responses. This was supported by a number of publications showing that the major immune cell subsets differ in their expression and co-expression levels in healthy subjects and in patients with immune-mediated diseases being also associated with inflammation severity [2,8,9].…”

Section: Introductionmentioning

confidence: 68%

CO-EXPRESSION OF MEMBRANE-BOUND TUMOR NECROSIS FACTOR-α RECEPTORS IN MAJOR SUBPOPULATIONS OF IMMUNOCOMPETENT CELLS IN HEALTHY INDIVIDUALS AND PATIENTS WITH RHEUMATOID ARTHRITIS AS WELL AS BRONCHIAL ASTHMA

et al. 2021

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A pleiotropic cytokine TNFα is an important inflammatory mediator of a number of diseases; its biological functions are fulfilled through two different receptors, TNFR1 and TNFR2. Changes in the ratio between these types of receptors shifting the balance between the pro-apoptotic and proliferation signaling pathways play a crucial role in eliciting the cell response to TNFα. The pathological processes in the body can alter the levels of TNFR1 and TNFR2 expression on the cells involved in disease development. Therefore, this study was aimed at investigating the level of co-expression of type 1 and 2 TNFα receptors in the major subpopulations of peripheral blood cells in patients with rheumatoid arthritis (RA) and bronchial asthma (BA). The greatest changes in the percentage of cells expressing TNFR1 and TNFR2 were revealed for the B-lymphocyte subpopulation. For the T-lymphocyte subpopulation, there were some differences in the percentage of cells expressing exclusively TNFR1 in RA and BA patients compared with those in healthy subjects, as well as between the RA and BA groups. A higher percentage of double-negative monocytes was observed in patients with BA and RA compared to healthy subjects. These findings indicate that the coexpression profile of TNFR1 and TNFR2 receptors in patients with RA and BA differ within these groups as well as compared to that in healthy subjects. These immune cell populations are actively involved in the pathogenesis of both rheumatoid arthritis and bronchial asthma, so the results may indicate that these cells might show different responses to TNFα as the percentage and the number of receptors on their surface vary.

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Section: Introductionmentioning

confidence: 68%

CO-EXPRESSION OF MEMBRANE-BOUND TUMOR NECROSIS FACTOR-α RECEPTORS IN MAJOR SUBPOPULATIONS OF IMMUNOCOMPETENT CELLS IN HEALTHY INDIVIDUALS AND PATIENTS WITH RHEUMATOID ARTHRITIS AS WELL AS BRONCHIAL ASTHMA

et al. 2021

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“…An interesting variant of receptor redistribution was demonstrated for naive cytotoxic T cells compared with the healthy donors: the proportion of cells with type 1 receptors was dramatically increased, while the percentage of cells expressing type 2 receptors was sharply reduced. Since type 1 and type 2 receptors implement different functions, these changes may indicate a change in the nature of the response of these cells to cytokines [11,12], and as a result, a change in their functional activity in RA. Evidence suggests that triggering a signal through type 1 and type 2 receptors simultaneously has significant therapeutic potential.…”

Section: Discussionmentioning

confidence: 99%

Co-Expression Profile of TNF Membrane-Bound Receptors Type 1 and 2 in Rheumatoid Arthritis on Immunocompetent Cells Subsets

Alshevskaya

Lopatnikova

Zhukova

et al. 2019

IJMS

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Introduction: Tumor necrosis factor (TNFα) is an important proinflammatory cytokine in rheumatoid arthritis (RA) immune processes. However, TNFα activity and functions may be regulated by soluble receptors, which act as decoys, and by number, density, and co-expression of its membrane-bound receptors type 1 and 2 (TNFR1 and TNFR2). The aim of this study was to reveal associations between TNFR1/2 co-expression profile parameters and RA disease activity indicators. Methods: PBMC were analyzed from 46 healthy donors and 64 patients with RA using flow cytometry. Patients were divided according to the disease activity score (DAS) 28 index into groups with high (n = 22, 34.4%), moderate (n = 30, 46.9%), and low (n = 12, 18.8%) disease activity. Co-expression of TNFR1 and TNFR2 was studied by evaluating the percentage of cells, with different receptors, and by counting the number of receptors of each type per cell, using QuantiBritePE beads. Associations between disease severity and activity indicators and parameters of TNFα receptor expression in subpopulations of immune cells were studied. Results: T cell subsets from RA patients were characterized by co-expression of TNFR1 and TNFR2, and were found to differ significantly compared with healthy donors. Memory cells both among T helper cells and cytotoxic T cells demonstrated the most significant differences in TNFR-expression profile. Multivariable logistic regression revealed model to identified RA patients from healthy individual based on the TNFR1/2 co-expression parameters. Conclusion: The profile of TNFR1\2 co-expression differs in RA comparing with health. Proportion of TNFR1+TNFR2- cells increased significantly among memory T helper cells and activated cytotoxic T cells, and decreased significantly among naïve cytotoxic T cells and T regulatory cells as compared with health. The parameters of TNFR1\2 co-expression in RA are associated with clinical and laboratory indicators of disease activity.

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“…However, fundamental questions regarding the effect of the distribution of different receptor types within a cell subpopulation on cellular functional activity, the threshold level of cellular responses after the binding of TNF-α to TNFRs, and whether switching between different signaling pathways by varying receptor expression density, remain unanswered. Previous studies reported variations in expression density and co-expression of TNFRs between the healthy cell populations and those under pathological conditions [6]. Nevertheless, the effects of these changes and their potential are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Ligand-Regulated Expression of TNF Receptors 1 and 2 Determines Receptor-Mediated Functional Responses

Alshevskaya

Koneva

Belomestnova

et al. 2021

Int Arch Allergy Immunol

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Introduction: Modulating specific biological effects through the changes in cytokine receptors’ expression level remains poorly understood. This study aimed to investigate the influence of the dose-dependent effect of TNF on the balance between proapoptotic and proliferation response depending on the parameters of TNFR1/2 expression density. Methods: Tumor cell lines (HEp-2, K-562, MCF-7, ZR-75/1, MOLT-4, IM-9, and Raji) were characterized for TNFR1/2 co-expression using flow cytometry and were studied to reveal the dose-dependent effect of rhTNF on cell cycle and apoptosis parameters. The associations among the studied parameters were estimated by correlation and regression analysis. Results: It was found for ZR-75/1 cells (the cell line characterized by high expression of both types) that a dose-dependent increase in expression of both types of TNF-α receptors on cells reduces the proliferative activity of cells. For MOLT-4 cells (which are characterized by lower expression), an increase in proliferative response of cells was positively associated with the percentage of both TNFR1+ and TNFR2+ cells. However, opposite effects on the cells were shown for the K-562 and MCF-7 lines having a similar expression profile. A similarity (a large percentage of double-positive cells) was revealed for the lines having similar effects (K-562 and ZR-75/1). Conclusions: High expression of TNF receptor type 1 is not always associated with predominant activation of proapoptotic pathways. However, in the case of simultaneous high expression of both types of receptors, the proportion of double-positive cells is crucial for the activation of either the proapoptotic or proliferation pathways.

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Expression Density of Receptors as a Potent Regulator of Cell Function and Property in Health and Pathology

Cited by 15 publications

References 70 publications

CO-EXPRESSION OF MEMBRANE-BOUND TUMOR NECROSIS FACTOR-α RECEPTORS IN MAJOR SUBPOPULATIONS OF IMMUNOCOMPETENT CELLS IN HEALTHY INDIVIDUALS AND PATIENTS WITH RHEUMATOID ARTHRITIS AS WELL AS BRONCHIAL ASTHMA

CO-EXPRESSION OF MEMBRANE-BOUND TUMOR NECROSIS FACTOR-α RECEPTORS IN MAJOR SUBPOPULATIONS OF IMMUNOCOMPETENT CELLS IN HEALTHY INDIVIDUALS AND PATIENTS WITH RHEUMATOID ARTHRITIS AS WELL AS BRONCHIAL ASTHMA

Co-Expression Profile of TNF Membrane-Bound Receptors Type 1 and 2 in Rheumatoid Arthritis on Immunocompetent Cells Subsets

Ligand-Regulated Expression of TNF Receptors 1 and 2 Determines Receptor-Mediated Functional Responses

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