Study of the potential of tolerogenic dendritic cells to immunophenotypic reversion affected by tumor necrosis factor
https://doi.org/10.51523/2708-6011.2025-22-2-08
Abstract
Objective. To assess reversion of tolerogenic dendritic cells (tolDC), obtained from human blood monocytes into immunogenic mature dendritic cells (mDC) under the influence of TNF-α.
Materials and methods. The immunophenotype of dendritic cells (DCs) obtained from blood monocytes of healthy donors (n=6) was assessed by flow cytometry: immature DC culture (immDC), mature (mDC) culture, tolDC culture, tolDC culture after exposure to the proinflammatory factor TNF-α (tol DCs/TNF-α). Statistical analysis was performed using nonparametric methods.
Results. There was 24.05(19.30-28.20) % of CD83+ cells in the population of mDCs, that was significantly higher compared with immDCs, tolDCs and tolDCs after stimulation with TNF-α (imm DCs – 4.10 (2.75-5.83), tol DCs – 4.45 (3.68-4.93), tol DCs/TNF-α – 9.70 (8.83-10.58). The intensity of HLA-DR expression on the surface of mDCs was significantly higher compared with immDCs, tolDCs and tolDCs after stimulation with TNF-α (imm DCs – 23.03 (18.24-25.40) RFI; tolDCs – 27.54 (25.04-32.41) RFI; tolDC – 10.56 (9.21-12.77) RFI; tolDC/TNF-α – 13.74 (10.66-18.53) RFI (RFI – relative fluorescence intensity).
Conclusion. Adding of the TNF-α as maturation inducer did not result in immunophenotypic reversion of tolDCs to the mDCs level. The obtained data indicate in favor of possibility to use safely tolDCs as a biomedical cell product for the treatment of diseases associated with an excessive immune response.
About the Authors
Ya. S. MinichBelarus
Yana S. Minich - Researcher at the Laboratory of Immunology and Virology, Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.
Minsk
A. Y. Hancharou
Belarus
Andrei Y. Hancharou - Candidate of Medical Sciences, Associate Professor, Director of the Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.
Minsk
N. G. Antonevich
Belarus
Natalia G. Antonevich - Candidate of Biological Sciences, Associate Professor, Leading Researcher at the Laboratory of Immunology and Virology, Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus.
Minsk
References
1. Adorini L, Giarratana N, Penna G. Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol. 2004;16:127-134. DOI: https://doi.org/10.1016/j.smim.2003.12.008
2. Piemonti L, Monti P, Sironi M, Fraticelli P, Leone BE, et al. Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol. 2000;164:4443-4451. DOI: https://doi.org/10.4049/jimmunol.164.9.4443
3. Svajger U, Rozman P. Induction of Tolerogenic Dendritic Cells by Endogenous Biomolecules: An Update. Frontiers in Immunology. 2018;9. DOI: https://doi.org/10.3389/fimmu.2018.02482
4. Svajger U, Rozman P. Tolerogenic dendritic cells: molecular and cellular mechanisms in transplantation. J Leukoc Biol. 2014;95:53-69. DOI: https://doi.org/10.1189/jlb.0613336
5. Bell GM, Anderson AE, Diboll J, Reece R, Eltherington O, Harry RA, et al. Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. Annals of the Rheumatic Diseases. 2017;76(1):227-234. DOI: https://doi.org/10.1136/annrheumdis-2015-208456
6. Hancharou A, Antonevich N, Chekan V. The influence of olfactory mucosa-derived mesenchymal stem cells on the antigenic profile of the dendritic cells. News of Biomedical Sciences. 2015;12(4):159-162. (In Russ.).
7. Hancharou A, Minich Y, Antonevich N. Immunomorphological characteristics of tolerogenic dendritic cells. News of Biomedical Sciences. 2024;24(3):182-194. (In Russ.).
8. Domogalla MP, Rostan PV, Raker VK, et al. Tolerance through education: how tolerogenic dendritic cells shape immunity. Frontiers in Immunology. 2017;8:1764. DOI: https://doi.org/10.3389/fimmu.2017.01764
9. Hilkens CMU, Isaacs JD. Tolerogenic dendritic cell therapy for rheumatoid arthritis: where are we now? Clinical & Experimental Immunology. 2013;172(2):148-157. DOI: https://doi.org/10.1111/cei.12038
10. Raker VK, Domogalla MP, Steinbrink K. Tolerogenic Dendritic Cells for Regulatory T Cell Induction in Man. Frontiers in Immunology. 2015;6:569. DOI: https://doi.org/10.3389/fimmu.2015.00569
11. Wu L, Liu YJ. Development of dendritic-cell lineages. Immunity. 2007;26(6):741-750. DOI: https://doi.org/10.1016/j.immuni.2007.06.006
12. Blanco P, Palucka AK, Pascual V, Banchereau J. Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev. 2008;19(1):41-52. DOI: https://doi.org/10.1016/j.cytogfr.2007.10.004
13. Trevejo JM, Marino MW, Philpott N, Josien R, et al. TNF-alpha -dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection. Proc Natl Acad Sci USA. 2001;98(21):12162-12167. DOI: https://doi.org/10.1073/pnas.211423598
14. Ritter U, Meissner A, Ott J, Körner H. Analysis of the maturation process of dendritic cells deficient for TNF and lymphotoxin-alpha reveals an essential role for TNF. J Leukoc Biol. 2003;74:216-222. DOI: https://doi.org/10.1189/jlb.1202587
15. Timohina O, Hancharou A, Antonevich N. Methods for obtaining dendritic cells for the treatment of cancer. News Of Biomedical Sciences. 2020;20(2):127-136. (In Russ.).
16. Riaz B, Islam SMS, Ryu HM, Sohn S. Regulates the Immune Responses in Inflammatory Disorders. Int J Mol Sci. 2023;24(3):2831. DOI: https://doi.org/10.3390/ijms24032831
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Review
For citations:
Minich Ya.S., Hancharou A.Y., Antonevich N.G. Study of the potential of tolerogenic dendritic cells to immunophenotypic reversion affected by tumor necrosis factor. Health and Ecology Issues. 2025;22(2):69-75. (In Russ.) https://doi.org/10.51523/2708-6011.2025-22-2-08