Content of T lymphocytes expressing ectonucleotidases CD39 and СD73 in ulcerative colitis
https://doi.org/10.31146/1682-8658-ecg-231-11-81-89
Abstract
The aim of the study was to evaluate the content of T-cells expressing ectonucleotidases CD39 and CD73, as well as their association with the mRNA level of ADORA2A gene encoding adenosine A2A receptor in the peripheral blood of ulcerative colitis (UC) patients in comparison with healthy donors. Material and Methods. The group of UC patients (n=18) and healthy donors (n=22) was examined. The content of lymphocytes carrying ectonucleotidases on their surface in peripheral blood was estimated by flow cytometry. The mRNA level of ADORA2A gene was analyzed by real-time PCR. Results. A higher content of activated CD8+CD25+ T-cells was registered in UC patients than in healthy subjects (5.85% (3.02-27.17) vs. 2.36% (1.35-3.12) at p=0.0008). Expression of ectonucleotidases on the surface of T-cells depended on their belonging to a certain subpopulation. It was noted that in UC patients the content of CD8+CD73+ T-cells was higher than in healthy individuals (29.29% (19.73-49.70) vs. 20.00% (8.01-27.41) at p=0.031). The increase in CD8+CD73+ T-cells in UC was accompanied by an increase in the number of activated CD8+CD25+ T-cells (rs=0.66, p=0.031). The level of ADORA2A mRNA was higher in UC patients than in healthy donors (0.415×103 (0.006×103-1.540×103) vs. 0.014×103 (0.005×103-0.046×103) at p=0.000025). ADORA2A mRNA levels did not correlate with the number of CD39+ and CD73+ T cells, nor did they correlate with the content of CD8+, CD4+ and Treg cells themselves. Conclusion. In UC patients, activated cytotoxic CD8+CD73+ T cells may play a significant role in the adenosineergic pathway.
About the Authors
G. A. Zhulai
Institute of Biology, Karelian Research Centre, Russian Academy of Sciences
Russian Federation
Russian Federation
L. V. Topchieva
Institute of Biology, Karelian Research Centre, Russian Academy of Sciences
Russian Federation
Russian Federation
D. A. Atorin
Institute of Biology, Karelian Research Centre, Russian Academy of Sciences
Russian Federation
Russian Federation
O. P. Dudanova
Petrozavodsk State University
Russian Federation
Russian Federation
I. V. Kurbatova
Institute of Biology, Karelian Research Centre, Russian Academy of Sciences
Russian Federation
Russian Federation
References
1. Shelygin Yu.A., Ivashkin V.T., Belousova E.A. et al. Ulcerative colitis (K51), adults. Koloproktologiâ. 2023;22(1):10-44. (In Russ) doi: 10.33878/2073-7556-2023-22-1-10-44.
2. Antonioli L., Fornai M., Pellegrini C., Bertani L., Nemeth Z.H., Blandizzi C. Inflammatory Bowel Diseases: It’s Time for the Adenosine System. Front Immunol. 2020;11:1310. doi: 10.3389/fimmu.2020.01310.
3. Pasquini S., Contri C., Borea P.A., Vincenzi F., Varani K. Adenosine and Inflammation: Here, There and Everywhere. IJMS. 2021;22(14):7685. doi: 10.3390/ijms22147685.
4. Ohta A., Sitkovsky M. Extracellular Adenosine-Mediated Modulation of Regulatory T Cells. Front Immunol. 2014;5. doi: 10.3389/fimmu.2014.00304.
5. Zhu Y., Zhuang Z., Wu Q. et al. CD39/CD73/A2a Adenosine Metabolic Pathway: Targets for Moxibustion in Treating DSS-Induced Ulcerative Colitis. Am J Chin Med. 2021;49(03):661-676. doi: 10.1142/S0192415X21500300.
6. Kim S.E., Ko I.G., Jin J.J. et al. Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats. BioMed Research International. 2020;2020:1-11. doi: 10.1155/2020/2169083.
7. Bahreyni A., Samani S.S., Khazaei M., Ryzhikov M., Avan A., Hassanian S.M. Therapeutic potentials of adenosine receptors agonists and antagonists in colitis; Current status and perspectives. Journal Cellular Physiology. 2018;233(4):2733-2740. doi: 10.1002/jcp.26073.
8. Beyazit Y., Koklu S., Tas A. et al. Serum adenosine deaminase activity as a predictor of disease severity in ulcerative colitis. Journal of Crohn’s and Colitis. 2012;6(1):102-107. doi: 10.1016/j.crohns.2011.07.010.
9. Dal Ben D., Antonioli L., Lambertucci C., Fornai M., Blandizzi C., Volpini R. Purinergic Ligands as Potential Therapeutic Tools for the Treatment of Inflammation-Related Intestinal Diseases. Front Pharmacol. 2018;9:212. doi: 10.3389/fphar.2018.00212.
10. Ercan G., Yigitturk G., Erbas O. Therapeutic effect of adenosine on experimentally induced acute ulcerative colitis model in rats. Acta Cir Bras. 2019;34(12): e201901204. doi: 10.1590/s0102-865020190120000004.
11. Rybaczyk L., Rozmiarek A., Circle K. et al. New bioinformatics approach to analyze gene expressions and signaling pathways reveals unique purine gene dysregulation profiles that distinguish between CD and UC: Inflammatory Bowel Diseases. 2009;15(7):971-984. doi: 10.1002/ibd.20893.
12. Ye J.H., Rajendran V.M. Adenosine: An immune modulator of inflammatory bowel diseases. WJG. 2009;15(36):4491. doi: 10.3748/wjg.15.4491.
13. Künzli B.M., Berberat P.O., Dwyer K. et al. Variable impact of CD39 in experimental murine colitis. Dig Dis Sci. 2011; 56: 1393-1403. doi: 10.1007/s10620-010-1425-9.
14. Friedman D.J., Künzli B.M., A-Rahim Y.I., Sevigny J., Berberat P.O., Enjyoji K. et al. CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. Proceedings of the National Academy of Sciences. 2009;106(39):16788-16793. doi: 10.1073/pnas.0902869106.
15. Longhi M.S., Moss A., Jiang Z.G., Robson S.C. Purinergic signaling during intestinal inflammation. J Mol Med. 2017;95(9):915-925. doi: 10.1007/s00109-017-1545-1.
16. Ye H., Zhao J., Xu X., Zhang D., Shen H., Wang S. Role of adenosine A2a receptor in cancers and autoimmune diseases. Immunity Inflam & Disease. 2023;11(4): e826. doi: 10.1002/iid3.826.
17. Borsellino G., Kleinewietfeld M., Di Mitri D. et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007;110(4):1225-1232. doi: 10.1182/blood-2006-12-064527.
18. Gibson D.J., Elliott L., McDermott E. et al. Heightened Expression of CD39 by Regulatory T Lymphocytes Is Associated with Therapeutic Remission in Inflammatory Bowel Disease. Inflammatory Bowel Diseases. 2015;21(12):2806-2814. doi: 10.1097/MIB. 0000000000000566.
19. Radygina T.V., Petrichuk S.V., Kuptsova D.G. et al. Content of CD4+ cells expressing CD39/CD73 ectonucleotidases in children with inflammatory bowel diseases. Bulletin of RSMU. 2022; (4): 17-23. doi: 10.24075/brsmu.2022.039.
20. Lord J.D., Shows D.M., Chen J., Thirlby R.C. Human Blood and Mucosal Regulatory T Cells Express Activation Markers and Inhibitory Receptors in Inflammatory Bowel Disease. Unutmaz D, ed. PLoS ONE. 2015;10(8): e0136485. doi: 10.1371/journal.pone.0136485.
21. Longhi M.S., Moss A., Bai A. et al. Characterization of Human CD39+ Th17 Cells with Suppressor Activity and Modulation in Inflammatory Bowel Disease. Hogan SP, ed. PLoS ONE. 2014;9(2): e87956. doi: 10.1371/journal.pone.0087956.
22. Libera J., Wittner M., Kantowski M. et al. Decreased Frequency of Intestinal CD39+γδ+ T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease. Front Immunol. 2020;11:567472. doi: 10.3389/fimmu.2020.567472.
23. Ferretti E., Horenstein A.L., Canzonetta C., Costa F., Morandi F. Canonical and non-canonical adenosinergic pathways. Immunology Letters. 2019;205:25-30. doi: 10.1016/j.imlet.2018.03.007.
24. Wang R., Wang Y., Wu C. et al. CD73 blockade alleviates intestinal inflammatory responses by regulating macrophage differentiation in ulcerative colitis. Exp Ther Med. 2023;25(6):272. doi: 10.3892/etm.2023.11972.
25. Doherty G.A., Bai A., Hanidziar D. et al. CD 73 is a phenotypic marker of effector memory T h17 cells in inflammatory bowel disease. Eur J Immunol. 2012;42(11):3062-3072. doi: 10.1002/eji.201242623.
26. Ohta A., Ohta A., Madasu M. et al. A2A Adenosine Receptor May Allow Expansion of T Cells Lacking Effector Functions in Extracellular Adenosine-Rich Microenvironments. The Journal of Immunology. 2009;183(9):5487-5493. doi: 10.4049/jimmunol.0901247.
27. Vuerich M., Nguyen D.H., Ferrari D., Longhi M.S. Adenosine-mediated immune responses in inflammatory bowel disease. Front Cell Dev Biol. 2024;12:1429736. doi: 10.3389/fcell.2024.1429736.
Review
For citations:
Zhulai G.A., Topchieva L.V., Atorin D.A., Dudanova O.P., Kurbatova I.V. Content of T lymphocytes expressing ectonucleotidases CD39 and СD73 in ulcerative colitis. Experimental and Clinical Gastroenterology. 2024;(11):81-89. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-231-11-81-89
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