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Production of Stem Cell Antigen 1 Sca-1/Ly-6A/E by Freshly Isolated NK Cells Cultured with Relevant Cytokines

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Activated NK cells in appropriate conditions are known to express stem cell antigen 1 (Sca-1/Ly-6A/E). To investigate its production, NK cells isolated from mouse spleens were incubated ex vivo in the presence of different combinations of cytokines (IL-12, IL-15, IL-18, and IFNγ). Expression of Sca-1 was found to be considerably higher in NK cells incubated in the presence of IL-18, IL-15, and IL-12 than in those treated with IL-15 and IL-18 only. To test the hypothesis that the effect of IL-12 was due to stimulation of IFNγ production, we replaced IL-12 with IFNγ in some samples and added specific anti-IFNγ antibody to some samples cultured with IL-15/IL-18+IL-12. In the subpopulations incubated in the presence of IL-15/IL-18 with added IFNγ instead of IL-12, the expression of Sca-1 was not increased. By contrast, in samples treated with IL-15/IL-18+IL-12 and anti-IFNγ antibody, the expression of Sca-1 was activated to a similar extent as in those stimulated by IL-15/IL-18+IL-12 combination without the antibody. The obtained data suggest that IL-12 activates the production of Sca-1 by NK cells through an IFNγ-independent mechanism.

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References

  1. Waldhauer I, Steinle A. NK cells and cancer immunosurveillance. Oncogene. 2008;27(45):5932-5943. https://doi.org/10.1038/onc.2008.267

    Article  CAS  Google Scholar 

  2. Stanley AC, Lacy P. Pathways for cytokine secretion. Physiology (Bethesda). 2010;25(4):218-229. https://doi.org/10.1152/physiol.00017.2010

    Article  CAS  Google Scholar 

  3. Fogel LA, Sun MM, Geurs TL, Carayannopoulos LN, French AR. Markers of nonselective and specific NK cell activation. J. Immunol. 2013;190(12):6269-6276. https://doi.org/10.4049/jimmunol.1202533

    Article  CAS  Google Scholar 

  4. Morcos MNF, Schoedel KB, Hoppe A, Behrendt R, Basak O, Clevers HC, Roers A, Gerbaulet A. SCA-1 Expression Level Identifies Quiescent Hematopoietic Stem and Progenitor Cells. Stem Cell Reports. 2017;8(6):1472-1478. https://doi.org/10.1016/j.stemcr.2017.04.012

    Article  CAS  Google Scholar 

  5. Whitmire JK, Eam B, Whitton JL. Mice deficient in stem cell antigen-1 (Sca1, Ly-6A/E) develop normal primary and memory CD4+ and CD8+ T-cell responses to virus infection. Eur. J. Immunol. 2009;39(6):1494-1504. https://doi.org/10.1002/eji.200838959

    Article  CAS  Google Scholar 

  6. Páral P, Faltusová K, Molík M, Renešová N, Šefc L, Nečas E. Cell cycle and differentiation of Sca-1+ and Sca-1— hematopoietic stem and progenitor cells. Cell. Cycle. 2018;17(16):1979-1991. https://doi.org/10.1080/15384101.2018.1502573

    Article  CAS  Google Scholar 

  7. Mitchell PO, Mills T, O’Connor RS, Kline ER, Graubert T, Dzierzak E, Pavlath GK. Sca-1 negatively regulates proliferation and differentiation of muscle cells. Dev. Biol. 2005;283(1):240-252. https://doi.org/10.1016/j.ydbio.2005.04.016

    Article  CAS  Google Scholar 

  8. Holmes C, Stanford WL. Concise review: stem cell antigen-1: expression, function, and enigma. Stem Cells. 2007;25(6):1339-1347. https://doi.org/10.1634/stemcells.2006-0644

    Article  CAS  Google Scholar 

  9. Okazawa A, Kanai T, Nakamaru K, Sato T, Inoue N, Ogata H, Iwao Y, Ikeda M, Kawamura T, Makita S, Uraushihara K, Okamoto R, Yamazaki M, Kurimoto M, Ishii H, Watanabe M, Hibi T. Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes. Clin. Exp. Immunol. 2004;136(2):269-276. https://doi.org/10.1111/j.1365-2249.2004.02431.x

    Article  CAS  Google Scholar 

  10. Nandagopal N, Ali AK, Komal AK, Lee SH. The Critical Role of IL-15-PI3K-mTOR Pathway in Natural Killer Cell Effector Functions. Front. Immunol. 2014;5:187. https://doi.org/10.3389/fimmu.2014.00187

    Article  CAS  Google Scholar 

  11. French AR, Holroyd EB, Yang L, Kim S, Yokoyama WM. IL-18 acts synergistically with IL-15 in stimulating natural killer cell proliferation. Cytokine. 2006;35(5-6):229-234. https://doi.org/10.1016/j.cyto.2006.08.006

    Article  CAS  Google Scholar 

  12. Oka N, Markova T, Tsuzuki K, Li W, El-Darawish Y, Pencheva-Demireva M, Yamanishi K, Yamanishi H, Sakagami M, Tanaka Y, Okamura H. IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18. Cancer Immunol. Immunother. 2020;69(9):1699-1712. https://doi.org/10.1007/s00262-020-02553-4

    Article  CAS  Google Scholar 

  13. He XS, Draghi M, Mahmood K, Holmes TH, Kemble GW, Dekker CL, Arvin AM, Parham P, Greenberg HB. T cell-dependent production of IFN-gamma by NK cells in response to influenza A virus. J. Clin. Invest. 2004;114(12):1812-1819. https://doi.org/10.1172/JCI22797

    Article  CAS  Google Scholar 

  14. El-Darawish Y, Li W, Yamanishi K, Pencheva M, Oka N, Yamanishi H, Matsuyama T, Tanaka Y, Minato N, Okamura H. Frontline Science: IL-18 primes murine NK cells for proliferation by promoting protein synthesis, survival, and autophagy. J. Leukoc. Biol. 2018;104(2):253-264. https://doi.org/10.1002/JLB.1HI1017-396RR

    Article  CAS  Google Scholar 

  15. de Araújo-Souza PS, Hanschke SC, Viola JP. Epigenetic control of interferon-gamma expression in CD8 T cells. J. Immunol. Res. 2015;2015:849573. https://doi.org/10.1155/2015/849573

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Medical University of Sofia, Sofia, Bulgaria

    Tz. Markova

  2. Department of Biology, Medical University of Sofia, Sofia, Bulgaria

    D. Dimitrova-Dikanarova & M. Markova

  3. Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria

    I. Sainova & V. Kolyovska

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  1. Tz. Markova
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  2. I. Sainova
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  3. V. Kolyovska
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  4. D. Dimitrova-Dikanarova
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  5. M. Markova
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Correspondence to Tz. Markova.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 174, No. 7, pp. 74-78, July, 2022

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Markova, T., Sainova, I., Kolyovska, V. et al. Production of Stem Cell Antigen 1 Sca-1/Ly-6A/E by Freshly Isolated NK Cells Cultured with Relevant Cytokines. Bull Exp Biol Med 174, 62–65 (2022). https://doi.org/10.1007/s10517-022-05649-2

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  • DOI: https://doi.org/10.1007/s10517-022-05649-2

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