GALECTIN-9 STIMULATES MATURATION AND TH1-POLARIZING ACTIVITY OF IFNΑ-INDUCED DENDRITIC CELLS

DOI: 10.22138/2500-0918-2024-21-4-467-478

T.V. Tyrinova¹,², O.Yu. Leplina¹, M.A. Tikhonova¹,
S.A. Schifon², E.R. Chernykh¹

¹FSBSI «Research Institute of Fundamental and Clinical Immunology»,
Novosibirsk, Russian Federation
²Novosibirsk State University, Novosibirsk, Russian Federation

Abstract. Galectin-9 (Gal-9) inhibits the T-cell immune response via ligation with the inhibitory checkpoint receptor TIM-3. Recent studies have demonstrated the expression of TIM-3 on myeloid cells, including dendritic cells (DCs). Therefore, DCs may also be targets for Gal-9’s regulatory effect. The current study aimed to investigate the effect of Gal-9 on monocyte-derived DCs generated in the presence of IFNα (IFN-DCs). Material and methods. DCs were generated by culturing the adherent fraction of healthy donor mononuclear cells in the presence of GM-CSF and IFNα for 4 days, followed by recombinant Gal-9 (10 μg/ml) for 24 h. Phenotypic analysis was performed by flow cytometry using fluorochrome-conjugated monoclonal antibodies. The allostimulatory and Th1/Th2-polarizing activity of IFN-DCs was assessed in a mixed culture of leukocytes with allogeneic mononuclear cells. Results. IFN-DCs, as well as monocytic precursors expressed the inhibitory checkpoint receptor TIM-3 at a high level. When Gal-9 was added to IFN-DC cultures, the number of immature CD14⁺CD83ˉ cells decreased (pW=0.017), the number of mature CD83⁺ DCs increased (pW=0.028), and the level of the costimulatory molecule CD86 increased (pW=0.01). In the presence of Gal-9, IFN-DCs had allostimulatory activity towards CD4⁺ and CD8⁺ T lymphocytes and were characterized by a significantly higher ability to induce IFNγ-producing CD3⁺CD4⁺ T lymphocytes. Conclusions. The obtained data indicate that Gal-9 stimulates the maturation of IFN-DCs and their functional activity.

Keywords: dendritic cells, interferon α, TIM-3, galectin-9, allostimulatory activity

There is no conflict of interest.
Contact details of the corresponding author:
Tamara V. Tyrinova
tyrinova@bk.ru
Received: 01.09.2024
For citation: Tyrinova T.V., Leplina O.Yu., Tikhonova M.A., Schifon S.A., Chernykh E.R. Galectin-9 stimulates maturation and Th1-polarizing activity of IFNα-induced dendritic cells. [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2024, Vol. 21, no. 4, pp. 467–478. DOI: 10.22138/2500-0918-2024-21-4-467-478 (In Russ)

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Auhtors

Tamara V. Tyrinova
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
DB, leader researcher of the Laboratory of cellular immunotherapy
Novosibirsk, Russian Federation
tyriova@bk.ru

Olga Yu. Leplina
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
DM, leader researcher of the Laboratory of cellular immunotherapy
Novosibirsk, Russian Federation
oleplina@mail.ru

Marina A. Tikhonova
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
PhD, senior researcher of the Laboratory of cellular immunotherapy
Novosibirsk, Russian Federation
matrix-59@mail.ru

Sofia A. Schifon
Novosibirsk State University
Student of Institute of Medicine and Psychology V.Zelman
Novosibirsk, Russian Federation
s.shsherbakova@g.nsu.ru

Elena R. Chernykh
Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)
DM, Professor, Corresponding Member of the Russian Academy of Sciences, head of laboratory of cellular immunotherapy
Novosibirsk, Russian Federation
ct_lab@mail.ru