FoxP3+ T-regulatory lymphocytes in adipose tissue of cardiac surgery patients with different severity of coronary atherosclerosis
https://doi.org/10.29001/2073-8552-2024-39-4-84-91
Abstract
Introduction. T-regulatory (T-reg) lymphocytes as the main modulators of immunity, present in ectopic adipose tissue focuses, may be involved in the pathogenesis of atherosclerosis. Currently there is a lack of data regarding T-reg lymphocyte counts, particularly in epicardial (EAT) and thymic adipose tissue (TAT) in patients with coronary atherosclerosis.
Aim: To study the contents of FoxP3+ T-regulatory lymphocytes of peripheral blood, epicardial and thymic adipose tissue in patients with coronary atherosclerosis.
Materials and Methods. The study included a total of 26 cardiosurgical profile patients with coronary atherosclerosis. Patients were divided into two groups via Gensini Score (GS): first group with severe coronary atherosclerosis (GS > 26.5; n = 15) and second group without severe coronary atherosclerosis (GS ≤ 26.5; n = 11). In all patients, the levels of FoxP3 nuclear translocation and the relative content of CD4+CD25hiFoxP3 and CD4+CD25loFoxP3 T-reg lymphocytes in peripheral blood, epicardial, thymic, and subcutaneous adipose tissue (SAT) were determined by flow cytometry with imaging.
Results. The group of patients with severe coronary atherosclerosis was characterised by a statistically significant higher median of relative content of CD4+CD25hiFoxP3 T-lymphocytes (12.0 (6.5; 17.4) vs. 6.82 (3.32; 12.4) %; p = 0.031) and statistically significant lower median of nuclear translocation level of FoxP3 in CD4+CD25hiFoxP3 T-lymphocytes in TAT (30.82 (18.50; 40.80) vs. 51.91 (25.9; 71.00) %; p = 0.048). Statistically significant correlations between FoxP3 T-reg lymphocyte parameters in different adipose depots and lipid spectrum markers (TC, HDL-C) were found. There were inverse correlations found between EAT and TAT, in particular, between the relative contents of T-reg lymphocytes and of the FoxP3 nuclear translocation level.
Conclusion. Patients with severe coronary atherosclerosis (GS > 26.5 points) were characterised by an increased relative content of CD4+CD25hiFoxP3 T-lymphocytes in thymic adipose tissue and a decreased level of FoxP3 nuclear translocation in this cell subpopulation compared to patients with moderate atherosclerosis (GS ≤ 26.5 points). Identified correlations between relative content of T-reg lymphocytes and the level of FoxP3 nuclear translocation in thymic and epicardial adipose tissues suggest potential existence of T-reg lymphocyte recirculation in-between these ectopic adipose depots.
Keywords
About the Author
A. A. DmitriukovRussian Federation
Alexey A. Dmitriukov, Junior Research Scientist, Clinical Diagnostic Laboratory
111a, Kievskaya str., Tomsk, 634012
References
1. AlZaim I., Hammoud S.H., Al-Koussa H. et al. Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases. J. Front. Cardiovasc. Med. 2020;7 17;7:1-40. DOI: 10.3389/fcvm.2020.602088.
2. Napoli G., Pergola V., Basile P., De Feo D., Bertrandino F., Baggiano A. et al. Epicardial and Pericoronary Adipose Tissue, Coronary Inflammation, and Acute Coronary Syndromes. J. Clin. Med. 2023 21;12(23):7212. DOI: 10.3390/jcm12237212.
3. Song Y., Tan Y., Deng M., et al. Epicardial adipose tissue, metabolic disorders, and cardiovascular diseases: recent advances classified by research methodologies. MedComm. 2023;4:e413. DOI: 10.1002/mco2.413.
4. Kologrivova, I.V, Naryzhnaya N.V., Koshelskaya O.A., Suslova T.E., Kravchenko E.S., Kharitonova O.A., Evtushenko V.V., Boshchenko A.A. Association of Epicardial Adipose Tissue Adipocytes Hypertrophy with Biomarkers of Low-Grade Inflammation and Extracellular Matrix Remodeling in Patients with Coronary Artery Disease. Biomedicines. 2023:17;11(2):241. DOI: 10.3390/biomedicines11020241.
5. Sivasami P., Li C. Derivation and Differentiation of Adipose-Tissue Regulatory T Cells: A Stepwise, Multi-Site Process. Front. Immunol. 2020;11:599277. DOI: 10.3389/fimmu.2020.599277.
6. Palatella M., Guillaume S.M., Linterman M.A., Huehn J. The dark side of Tregs during aging. Front Immunol. 2022;13:940705. DOI: 10.3389/fimmu.2022.940705
7. Yu Y., Bai H., Wu F., Chen J., Li B., Li Y.. Tissue adaptation of regulatory T cells in adipose tissue. Eur J Immunol. 2022;52(12):1898-1908. DOI: 10.1002/eji.202149527.
8. Magg T., Mannert J., Ellwart J.W., Schmid I., Albert M.H. Subcellular localization of FOXP3 in human regulatory and nonregulatory T cells. Eur J Immunol. 2012;42(6):1627-38. DOI: 10.1002/eji.201141838.
9. Lemarquis A.L.L., Kousa A., Argyropoulos K.V., Jahn L., Gipson B., Serrano-Marin L., Andrlova H., Tsai J., Dudakov J.A., DeWolf S., Brink M.; Recirculating Regulatory T Cells Mediate Thymic Regeneration in a ZFP36L1 and Amphiregulin Dependent Manner. Blood 2023; 142 (Supplement 1): 457. DOI: 10.1182/blood-2023-183036.
10. Kologrivova I.V., Suslova T.E., Koshelskaya O.A., Kharitonova O.A., Trubacheva O.A., Kravchenko E.S. Circulating FoxP3+ T-lymphocytes in chronic coronary artery disease: Associations with the severity of atherosclerosis and lipid metabolism. The Siberian Journal of Clinical and Experimental Medicine. 2021;36(2):45–51. DOI: 10.29001/2073-8552-2021-36- 2-45-51.
11. Charaix J., Borelli A., Santamaria J.C., Chasson L., Giraud M., Sergé A., Irla M. Recirculating Foxp3+ regulatory T cells are restimulated in the thymus under Aire control. Cell Mol Life Sci. 2022;79(7):355. DOI: 10.1007/s00018-022-04328-9.
12. Dooley J., Liston A. Molecular control over thymic involution: from cytokines and microRNA to aging and adipose tissue. Eur J Immunol. 2012;42(5):1073-9. DOI: 10.1002/eji.201142305.
13. Kozlov V.A. Determining role of thymus in immune pathogenesis of autoimmune, oncological and infectious diseases. Medical Immunology (Russia). 2023;25(1):39–58. (In Russ.). DOI: 10.15789/1563-0625-DRO-2591.
14. Dai X., Zhang D., Wang C. et al. The Pivotal Role of Thymus in Atherosclerosis Mediated by Immune and Inflammatory Response. Int J Med Sci. 2018 20;15(13):1555-1563. DOI: 10.7150/ijms.27238.
15. Palatella M., Guillaume S.M., Linterman M.A. et al The dark side of Tregs during aging. Front. Immunol. 2022;13:940705. DOI: 10.3389/fimmu.2022.940705
16. Thiault N., Darrigues J., Adoue V., Gros M., Binet B., Perals C., Leobon B., Fazilleau N., Joffre O.P., Robey E.A., van Meerwijk J.P.M., Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat. Immunol. 2015;16(6):628-34. DOI: 10.1038/ni.3150.
17. Rueda C.M., Rodríguez-Perea A.L., Moreno-Fernandez M., Jackson C.M., Melchior J.T., Davidson W.S., Chougnet C.A. High density lipoproteins selectively promote the survival of human regulatory T cells. J Lipid Res. 2017;58(8):1514-1523. DOI: 10.1194/jlr.M072835.
18. Atehortua L., Davidson W.S., Chougnet C.A. Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties. Arterioscler Thromb Vasc Biol. 2024;44(6):1191-1201. DOI: 10.1161/ATVBAHA.124.320851.
19. Saravia J., Zeng H., Dhungana Y., Bastardo Blanco D., Nguyen T.M., Chapman N.M., Wang Y., Kanneganti A., Liu S., Raynor J.L., Vogel P., Neale G., Carmeliet P., Chi H. Homeostasis and transitional activation of regulatory T cells require c-Myc. Sci Adv. 2020;6(1):eaaw6443. DOI: 10.1126/sciadv.aaw6443.
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For citations:
Dmitriukov A.A. FoxP3+ T-regulatory lymphocytes in adipose tissue of cardiac surgery patients with different severity of coronary atherosclerosis. Siberian Journal of Clinical and Experimental Medicine. 2024;39(4):84-91. (In Russ.) https://doi.org/10.29001/2073-8552-2024-39-4-84-91