Galectin-9/Tim-3-dependent mechanism of regulation of functional activity of natural killers during pregnancy

Article Sidebar

pdf (Русский)
Published: Dec 15, 2023
DOI: https://doi.org/10.17072/1994-9952-2023-4-403-413
Keywords:
galectin-9, NK cells, Tim-3, immune tolerance, pregnancy.

Main Article Content

Ekaterina G. Orlova
Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia
Olga A. Loginova
Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia
Olga L. Gorbunova
Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia
Sergey V. Shirshev
Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia

Abstract

Galectins are a family of β-galactoside-binding low molecular weight proteins (lectins) homologous in the amino acid sequence of the carbohydrate-binding site. Galectins interact with glycans on the cell surface and are involved in regulating the functional activity of most cells of the human body. Galectin-9 plays a crucial role in controlling the functions of cells of the immune system. Of particular importance are the immunoregulatory effects of galectin-9 during pregnancy, when its production by trophoblast cells increases significantly, which is associated with the formation of peripheral immune tolerance. The main ligand for galectin-9 is the Tim-3 (T-cell immunoglobulin and mucin domain 3) molecule, whose high expression is detected on natural killers (NK cells). During pregnancy, the phenotype and functions of NK cells change significantly, which is necessary to prevent cytotoxic reactions to fetal cells. The review systematizes data on the role of galectin-9 in Tim-3-mediated regulation of NK cell functions in the aspect of pregnancy. The study of the regulation of the functional activity of NK cells is necessary to increase the effectiveness of NK cell therapy.
 

Article Details

How to Cite
Orlova Е. Г., Loginova О. А. ., Gorbunova О. Л. ., & Shirshev С. В. . (2023). Galectin-9/Tim-3-dependent mechanism of regulation of functional activity of natural killers during pregnancy. Bulletin of Perm University. Biology, (4), 403–413. https://doi.org/10.17072/1994-9952-2023-4-403-413
Issue
No. 4 (2023): Bulletin of Perm University. BIOLOGY
Section
Иммунология

License agreement

 

Author Biographies

Ekaterina G. Orlova, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia

Doctor of biology, leading researcher of laboratory of immunoregulation

Olga A. Loginova, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia

Сandidate of biology, junior researcher of laboratory of immunoregulation

Olga L. Gorbunova, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia

Candidate of biology, researcher of laboratory of immunoregulation

Sergey V. Shirshev, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the RAS, Perm, Russia

Doctor of medical sciences, head of laboratory of immunoregulation

References

Рапопорт Е.М., Бовин Н.В. Специфичность галектинов человека в составе клеток // Биохимия. 2015. Т. 80, № 7. С. 1010–1022.

Рапопорт Е.М., Курмышкина О.В., Бовин Н.В. Галектины млекопитающих: структура, углеводная специфичность и функции // Биохимия. 2008. Т. 73, № 4. С. 483–497.

Asakura H. et al. Selective eosinophil adhesion to fibroblast via IFN-gamma-induced galectin-9 // J. Immunol. 2002. Vol. 169. P. 5912–5918.

Boron D.G. et al. Galectin-1 and galectin-9 concentration in maternal serum: implications in pregnancies complicated with preterm prelabor rupture of membranes // Journal of Clinical Medicine. 2022. Vol. 11, № 21. Р. 6330.

Cerdeira A.S. et al. Conversion of peripheral blood NK cells to a decidual NK-like phenotype by a cocktail of defined factors // J. of immunol. 2013. Vol. 190, № 8. P. 3939–3948.

Chen H. et al. T-cell immunoglobulin and mucin-domain containing-3 (TIM-3): Solving a key puzzle in autoimmune diseases // Intern. immunopharmacol. 2023. Vol. 121. P. 110418.

Cocker A.T.H. et al. CD56-negative NK cells: frequency in peripheral blood, expansion during HIV-1 infection, functional capacity and KIR expression. // Frontiers in Immunology. 2022. Vol. 13. P. 992723.

Crespo A.C. et al. Decidual NK cells transfer granulysin to selectively kill bacteria in trophoblasts // Cell. 2020. Vol. 182, № 5. P. 1125–1139.

Dixit A., Karande A.A. Glycodelin regulates the numbers and function of peripheral natural killer cells // J. Reprod. Immunol. 2020. Vol. 137. P. 102625.

Elahi S. et al. Galectin-9 binding to tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection // Blood. 2012. Vol. 119, № 18. P. 4192–204.

Enninga E.A.L. et al. Immune checkpoint molecules soluble program death ligand 1 and galectin-9 are increased in pregnancy // Am. J. of Reprod. Immunol. 2018. Vol. 79, № 2. e12795.

Erlebacher A. Immunology of the maternal-fetal interface // Annu. Rev. Immunol. 2013. Vol. 31. P. 387–411.

Fu B. et al. Natural killer cells promote fetal development through the secretion of growth-promoting factors // Immunity. 2017. Vol. 47, № 6. P. 1100–1113.

Fuselier C. et al. Placental galectins in cancer: why we should pay more attention // Cells. 2023. Vol. 12, № 3. P. 437.

Gleason M.K. et al. Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9 // Blood. 2012. Vol. 119, № 13. Р. 3064–3072.

Grossman T.B. et al. Soluble T cell immunoglobulin mucin domain 3 (sTim-3) in maternal sera: a potential contributor to immune regulation during pregnancy // The J. of maternal-fetal & neonatal medicine: the official J of the Europ. Associat. of Perinat. Med. 2021. Vol. 34, № 24. P. 4119–4122.

Han G. et al. Tim-3: an activation marker and activation limiter of innate immune cells // Front. Immunol. 2013. Vol. 4. P. 449–455.

Imaizumi T. et al. Interferon-gamma stimulates the expression of galectin-9 in cultured human endothelial cells // J. Leukoc. Biol. 2002. Vol. 72. P. 486–491.

Iwasaki-Hozumi H. et al. Blood levels of galectin-9, an immuno-regulating molecule, reflect the severity for the acute and chronic infectious diseases // Biomolecules. 2021. Vol. 11, № 3. P. 430.

Koopman L.A. et al. Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential // The J. of exp. medicine. 2003. Vol. 198, № 8. P. 1201–1212.

Li Y. et al. The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal-fetal interface in early pregnancy // Cellular & molecul. Immunol. 2016. Vol. 13, № 1. Р. 73–81.

Li Y. et al. Tim-3 signaling in peripheral NK cells promotes maternal-fetal immune tolerance and alleviates pregnancy loss // Science signaling. 2017. Vol. 10, № 498. P. 4323.

Lu C. et al. An emerging role of TIM3 expression on T cells in chronic kidney inflammation // Front. Immunol. 2021. Vol. 12. P. 798683.

Meggyes M. et al. Peripheral blood TIM-3 positive NK and CD8+T cells throughout pregnancy: TIM-3/Galectin-9 interaction and its possible role during pregnancy // PLoS One. 2014. Vol. 9, № 3. P. 92371.

Miko E. et al. Involvement of Galectin-9/TIM-3 Pathway in the Systemic Inflammatory Response in Early-Onset Preeclampsia // PLoS One. 2013. Vol. 8, № 8. P. 71811.

Nagahara K. et al. Galectin-9 increases Tim-3dendritic cells and CD8 T cells and enhances anti-tumor immunity via galection-9-Tim-3 interactions // J. Immunol. 2008. Vol. 181, № 11. P. 7660–7669.

Ndhlovu L.C. et al. Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity // Blood. 2012. Vol. 119, № 16. Р. 3734–3743.

Ocana-Guzman R., Torre-Bouscoulet L., Sada-Ovalle I. TIM-3 regulates distinct functions in macrophages // Front. Immunol. 2016. Vol. 13, № 7. Р. 229.

Orlova E.G. et al. Expression of TIM-3 and CD9 molecules on natural killer cells (NK) and T-lymphocytes with NK functions (NKT) in the peripheral blood at different trimesters of physiological pregnancy // J. Evol. Biochem. Phys. 2023a. Vol. 59. P. 809–821.

Orlova E.G. et al. Galectin-9 influences the Tim-3 molecule expression in natural killer different subpopulations // Med. Immunol. (Russia). 2023b. Vol. 25, № 3. P. 469–476.

Orlova E.G. et al. Hormone-Dependent Reprogramming of NK Cell Functions in the Aspect of Pregnancy // Science and Global Challenges of the 21st Century – Innovations and Technologies in Interdisciplinary Applications. Perm Forum 2022. Lecture Notes in Networks and Systems. 2023c. Vol. 622. Springer, Cham.

Pełech A. et al. Do Serum galectin-9 levels in women with gestational diabetes and healthy ones differ before or after delivery? A pilot study // Biomolecules. 2023. Vol. 13, № 4. P. 697.

Sanchez-Fueyo A. et al. Tim-3 inhibits T helper type 1-mediated auto- and allo- immune responses and promotes immunological tolerance // Nat. Immunol. 2003. Vol. 4, № 11. P. 1093–1101.

Shirshev S.V. et al. Hormonal regulation of NK cell cytotoxic activity // Dokl. Biol. Sci. 2017b. Vol. 472, № 1. P. 28–30.

Shirshev S.V. et al. MicroRNA in hormonal mechanisms of regulation of NK cell function // Dokl. Biochem. Biophys. 2017a. Vol. 474, № 1. P. 168–172.

So E.C. et al. NK cell expression of Tim-3: first impressions matter // Immunobiology. 2019. Vol. 224, № 3. Р. 362–370.

Song Yan et al. The mTORC1 signaling support cellular metabolism to dictate decidual NK cells function in early pregnancy // Front Immunol. 2022. Vol. 13. P. 771732.

Sun J. et al. Tim-3 is up regulated in NK cells during early pregnancy and inhibits NK cytotoxicity toward trophoblast in galectin-9 dependent pathway // PloS one. 2016. Vol. 11, № 1. P. 0147186.

Tang R., Rangachari M., Kuchroo V.K. Tim-3: A co-receptor with diverse roles in T cell exhaustion and tolerance // Semin. Immunol. 2019. Vol. 42. P. 101302.

Wang F. et al. Activation of Tim-3–Galectin-9 pathways improves survival of fully allergenic skin grafts // Transpl. Immunol. 2008. Vol. 19, № 1. P. 12–19.

Wu M. et al. Soluble co stimulatory molecule sTim3 regulates the differentiation of Th1and Th2 in patients with unexplained recurrent spontaneous abortion // Int. J. Clin. Exp. Med. 2015. Vol. 8, № 6. Р. 8812–8819.

Zhu C. et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity // Nat. Immunol. 2005. Vol. 6, № 12. P. 1245–1252.

Zhu W. et al. Tim-3: An inhibitory immune checkpoint is associated with maternal-fetal tolerance and recurrent spontaneous abortion // Clin. Immunol. 2022. Vol. 245. P. 109185.