Influence of Intracellular Regulation of Metabolism on the Population Composition of Peripheral Blood Lymphocytes
DOI:
https://doi.org/10.37482/2687-1491-Z155Keywords:
HIF-1α, SIRT3, adenosine triphosphate (ATP), cellular immunity, lymphocyte populations, immunometabolismAbstract
Metabolic activity has a significant impact on the differentiation, proliferation and functioning of T cells. Different lymphocyte subpopulations use, to varying degrees, glycolysis and mitochondrial metabolism, whose main regulators are hypoxia-inducible factor 1-alpha (HIF-1α) and sirtuin 3 (SIRT3), respectively. The purpose of this paper was to study changes in the population composition of peripheral blood lymphocytes in humans depending on the level of the intracellular metabolic regulators SIRT3 and HIF-1α. Materials and methods. 227 residents of the city of Arkhangelsk and the Arkhangelsk Region were examined (mean age 42 ± 11 years). Absolute lymphocyte count was determined using the Sysmex XS 500i haematology analyser, while CD3+, CD4+, CD8+, CD10+, CD25+ and CD95+ phenotypes content, by indirect immunoperoxidase reaction. Intracellular adenosine triphosphate (ATP) concentration was measured using the luciferase bioluminescence method. HIF-1α and SIRT3 concentrations were measured in lymphocyte lysate using enzyme immunoassay. To divide the total sample into groups according to SIRT3 and HIF-1α content, k-means clustering was utilized. Results. Changes in SIRT3 and HIF-1α intracellular concentrations correlated with ATP concentration. It was found that in the group with high HIF-1α content, the proportion of CD4+, CD8+, CD10+ and CD25+ lymphocytes was greater than in the group with high SIRT3 concentration, which had a greater proportion of CD95+ lymphocytes. Thus, the content of intracellular metabolic regulators that regulate ATP production pathways in the cell, i.e. oxidative phosphorylation (SIRT3) and glycolysis (HIF-1α), affects the population composition of lymphocytes and is therefore important for assessing the immune response.
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References
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Biswas S., Troy H., Leek R., Chung Y.-L., Li J.-L., Raval R.R., Turley H., Gatter K., Pezzella F., Griffiths J.R., Stubbs M., Harris A.L. Effects of HIF-1α and HIF2α on Growth and Metabolism of Clear-Cell Renal Cell Carcinoma 786-0 Xenografts. J. Oncol., 2010, vol. 2010. Art. no. 757908. DOI: 10.1155/2010/757908
Yu W., Denu R.A., Krautkramer K.A., Grindle K.M., Yang D.T., Asimakopoulos F., Hematti P., Denu J.M. Loss of SIRT3 Provides Growth Advantage for B Cell Malignancies. J. Biol. Chem., 2016, vol. 291, no. 7, pp. 3268–3279. DOI: 10.1074/jbc.M115.702076
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Neeli P.K., Gollavilli P.N., Mallappa S., Hari S.G., Kotamraju S. A Novel Metadherinδ7 Splice Variant Enhances Triple Negative Breast Cancer Aggressiveness by Modulating Mitochondrial Function via NFĸB-SIRT3 Axis. Oncogene, 2020, vol. 39, no. 10, pp. 2088–2102. DOI: 10.1038/s41388-019-1126-6
