Metabolic regulation of natural killer functions

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Published: Mar 29, 2023
DOI: https://doi.org/10.17072/1994-9952-2023-1-83-94
Keywords:
NK cells metabolism decidual phenotype immune tolerance pregnancy

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Ekaterina G. Orlova
Institute of Ecology and Genetics of Microorganisms UB RAS – branch of Perm Federal Research Center UB RAS; Perm, Russia
https://orcid.org/0000-0003-1195-8962

Abstract

Changes in the body metabolism affect the metabolic and functional activity of cells of the immune system. Pregnancy is characterized by changes in hormone production, basal metabolism, immunoreactivity, increase of fat mass. During pregnancy, NK cells acquire a regulatory phenotype, migrate to the uterus and become the dominant subpopulation of lymphocytes in uterus (decidual NK), which is necessary to maintain the invasive syncytiotrophoblast growth. This transformation into decidual NK cells is accompanied by increased glucose consumption and a predominant transition from oxidative phosphorylation to glycolysis. The key molecules involved in controlling the implementation of metabolic programs of NK cells are the target for rapamycin in mammalian cells (mTOR) and AMP-activated protein kinase (AMPK). The modularization of mTOR and AMPK activity by various agents (hormones, cytokines) during pregnancy determines the metabolic reprogramming of the NK cell phenotype and functions. The study of the metabolic regulation of the NK functional activity is necessary to increase the effectiveness of NK cell therapy.

Article Details

How to Cite
Orlova Е. Г. . (2023). Metabolic regulation of natural killer functions. Bulletin of Perm University. Biology, (1), 83–94. https://doi.org/10.17072/1994-9952-2023-1-83-94
Issue
No. 1 (2023): Bulletin of Perm University. BIOLOGY
Section
Иммунология

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Author Biography

Ekaterina G. Orlova, Institute of Ecology and Genetics of Microorganisms UB RAS – branch of Perm Federal Research Center UB RAS; Perm, Russia

Doctor of biology, Leading Researcher of the Laboratory of Immunoregulation; Senior Lecturer at the Department of Microbiology and Immunology

References

Орлова Е.Г. и др. Особенности экспрессии молекул Tim-3, CD9, CD49a лимфоцитами периферической крови при физиологической беременности // Вестник уральской медицинской академической науки. 2022. Т. 19, № 5. C. 461–473,

Allan D.S. et al. TGF-β affects development and differentiation of human natural killer cell subsets // Eur. J. Immunol. 2010. Vol. 40(8). P. 2289–2295.

Assmann N. et al. Srebp-controlled glucose metabolism is essential for NK cell functional responses // Nat. Immunol. 2017. Vol. 18. P. 1197–1206.

Béziat V. et al. NK cell terminal differentiation: correlated stepwise decrease of NKG2A and acquisition of KIRs // PLoS One. 2010. Vol. 5(8). e11966.

Björkström N.K., Ljunggren H.G., Michaëlsson J. Emerging insights into natural killer cells in human pe-ripheral tissues // Nat. Rev. Immunol. 2016. Vol. 16(5). P. 310–320.

Carlino C. et al. Recruitment of circulating NK cells through decidual tissues: a possible mechanism con-trolling NK cell accumulation in the uterus during early pregnancy // Blood. 2008. Vol. 111(6). P. 3108–3115.

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.

Chapman N.M., Shrestha S., Chi H. Metabolism in Immune Cell Differentiation and Function // Adv. Exp. Med. Biol. 2017. Vol. 1011. P. 1–85.

Chiossone L. et al. Maturation of mouse NK cells is a 4-stage developmental program // Blood. 2009. Vol. 113(22). P. 5488–5496.

Chiossone L. et al. In vivo generation of decidual natural killer cells from resident hematopoietic progeni-tors // Haematologica. 2014. Vol. 99(3). P. 448–457.

Crespo Â.C., et al. Decidual NK Cells Transfer Granulysin to Selectively Kill Bacteria in Trophoblasts // Cell. 2020. Vol. 182(5). P. 1125–1139.

Donnelly R.P. et al. mTORC1-dependent metabolic reprogramming is a prerequisite for NK cell effector function // J. Immunol. 2014. Vol. 193. P. 4477–4484.

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.

Husain Z., Seth P., Sukhatme V.P. Tumor-derived lactate and myeloid-derived suppressor cells: Linking metabolism to cancer immunology // Oncoimmunology. 2013. Vol. 2(11). e26383.

Jiang L. et al. Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells // International journal of biological sciences. 2021. Vol. 17(15). P. 4377–4395.

Jin X. et al. Decidualization-derived cAMP regulates phenotypic and functional conversion of decidual NK cells from CD56dimCD16- NK cells // Cell Mol. Immunol. 2021. Vol. 18(6). P. 1596–1598.

Keating S.E. et al. Metabolic reprogramming supports IFN-γ production by CD56bright NK cells // J. Im-munol. 2016. Vol. 196(6). P. 2552–2560.

Keskin D.B. et al. TGF beta promotes conversion of CD16+ peripheral blood NK cells into CD16- NK cells with similarities to decidual NK cells // Proc. Natl. Acad. Sci. USA. 2007. Vol. 104(9). P. 3378–3383.

Kim K.Y. et al. Adiponectin is a negative regulator of NK cell cytotoxicity // J. Immunol. 2006. Vol. 176(10). P. 5958–5664.

Koopman L.A. et al. Human decidual natural killer cells are a unique NK cell subset with immunomodu-latory potential // The J. of exp. medicine. 2003. Vol. 198(8). P. 1201–1212.

Lee C.L. et al. Glycodelin-A stimulates the conversion of human peripheral blood CD16-CD56bright NK cell to a decidual NK cell-like phenotype // Hum. Reprod. 2019. Vol. 34(4). P. 689–701.

Marcais A. et al. The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the de-velopment and activation of NK cells // Nat. Immunol. 2014. Vol. 15. P. 749–757.

Martrus G. et al. Proliferative capacity exhibited by human liver-resident CD49a+CD25+NK cells // PloS One. 2017. Vol. 12(8), e0182532.

Melsen J.E. et al. Human Circulating and Tissue-Resident CD56(bright) Natural Killer Cell Populations // Front. Immunol. 2016. Vol. 7. P. 262.

Montaldo E. et al. Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in hu-mans and mice // Eur. J. Immunol. 2015. Vol. 45(8). P. 2171–2182.

Moretta A. et al. Natural cytotoxicity receptors that trigger human NK-cell-mediated cytolysis // Immu-nol. Today. 2000. Vol. 21(5). P. 228–234.

Muller-Durovic B. et al. Killer cell lectin-like receptor G1 inhibits NK cell function through activation of adenosine 5′-monophosphateactivated protein kinase // J. Immunol. 2016. Vol. 197(7). P. 2891–2899.

Nandagopal N. et al. The Critical Role of IL-15-PI3K-mTOR Pathway in Natural Killer Cell Effector Functions // Front Immunol. 2014. Vol. 5. P. 187.

O'Brien K.L., Finlay D.K. Immunometabolism and natural killer cell responses // Nat. Rev. Immunol. 2019. Vol. 19(5). P. 282–290.

Poli A. et al. CD56bright natural killer (NK) cells: an important NK cell subset // Immunology. 2009. Vol. 126(4). P. 458–465.

Saito S. et al. The balance between cytotoxic NK cells and regulatory NK cells in human pregnancy // J. of Reprod. Immunol. 2008. Vol. 77(1), P. 14–22.

Salzberger W. et al. Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71 // PLoS One. 2018. Vol. 13. e0201170.

Sánchez-Rodríguez E.N. et al. Persistence of decidual NK cells and KIR genotypes in healthy pregnant and preeclamptic women: a case-control study in the third trimester of gestation // Reprod. Boil. and endocrinol. 2011. Vol. 9. P. 8.

Shojaei Z. et al. Functional prominence of natural killer cells and natural killer T cells in pregnancy and infertility: A comprehensive review and update // Pathol. Res. Pract. 2022. Vol. 238. P. 154062.

Slattery K. et al. TGFβ drives NK cell metabolic dysfunction in human metastatic breast cancer // J. Im-munother. Cancer. 2021. Vol. 9(2). e002044.

Song Yan et al. The mTORC1 Signaling Support Cellular Metabolism to Dictate Decidual NK Cells Func-tion in Early Pregnancy // Front Immunol. 2022. Vol. 13. P. 771732.

Sotnikova N. et al. Interaction of decidual CD56+ NK with trophoblast cells during normal pregnancy and recurrent spontaneous abortion at early term of gestation // Scandinavian journal of immunology. 2014. Vol. 80(3), P. 198–208.

Sun 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). e0147186.

Tessmer M.S. et al. KLRG1 binds cadherins and preferentially associates with SHIP-1 // Int. Immunol. 2007. Vol. 19(4). P. 391–400.

Vacca P. et al. Origin, phenotype and function of human natural killer cells in pregnancy // Trends Im-munol. 2011. Vol. 32. P. 517–523.

van den Heuvel M.J. et al. Trafficking of circulating pro-NK cells to the decidualizing uterus: regulatory mechanisms in the mouse and human // Immunol. Invest. 2005. Vol. 34(3). P. 273–293.

Viel S. et al. TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway // Sci. Signal. 2016. Vol. 9(415). ra19.

Wang Z. et al. (). IL-10 Enhances Human Natural Killer Cell Effector Functions via Metabolic Repro-gramming Regulated by mTORC1 Signaling // Frontiers in immunology. 2021. Vol. 12. P. 619195.

Yan S. et al. The mTORC1 Signaling Support Cellular Metabolism to Dictate Decidual NK Cells Function in Early Pregnancy // Frontiers in immunology.2022. Vol. 13. P. 771732.

Yan W.H. et al. Possible roles of KIR2DL4 expression on uNK cells in human pregnancy // Am. J. Re-prod. Immunol. 2007. Vol. 57(4). P. 233–242.

Zaiatz-Bittencourt V., Finlay D.K., Gardiner C.M. Canonical TGF-b signaling pathway represses human NK cell metabolism // J. Immunol. 2018. Vol. 200. P. 3934–3941.