| Title: | Different glycosylation profiles of cystatin F alter the cytotoxic potential of natural killer cells |
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| Authors: | ID Senjor, Emanuela, Institut "Jožef Stefan" (Author)
ID Pirro, Martina (Author)
ID Švajger, Urban (Author)
ID Prunk, Mateja, Institut "Jožef Stefan" (Author)
ID Sabotič, Jerica, Institut "Jožef Stefan" (Author)
ID Jewett, Anahid (Author)
ID Hensbergen, Paul J. (Author)
ID Perišić, Milica, Institut "Jožef Stefan" (Author)
ID Kos, Janko, Institut "Jožef Stefan" (Author) |
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| Files: |  PDF - Presentation file, download (3,96 MB)
MD5: 04686CF42F24E7542363D4B4ED34082F
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  IJS - Jožef Stefan Institute
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| Abstract: | Cystatin F, a cysteine peptidase inhibitor, is a potent modulator of NK cytotoxicity. By inhibiting granule-mediated cytotoxicity pathway, cystatin F induces formation of non-functional NK cell stage, called split-anergy. We show that N-glycosylation determines the localization and cellular function of cystatin F. Cystatin F mostly exhibited high-mannose glycosylation in U-937 cells, both high-mannose and complex glycosylation in NK-92 and primary NKs, and predominantly complex glycosylation in super-charged NKs. Manipulating N-glycosylation with kifunensine increased high-mannose glycosylation of cystatin F and lysosome localisation, which decreased cathepsin C activity and reduced NK cytotoxicity. Mannose-6-phosphate could significantly reduce the internalization of extracellular cystatin F. By comparing NK cells with different cytotoxic potentials, we found that high-mannose cystatin F was strongly associated with lysosomes and cathepsin C in NK-92 cell line. In contrast, in highly cytotoxic super-charged NKs, cystatin F with complex glycosylation was associated with the secretory pathway and less prone to inhibit cathepsin C. Modulating glycosylation to alter cystatin F localisation could increase the cytotoxicity of NK cells, thereby enhancing their therapeutic potential for treating cancer patients. |
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| Keywords: | cystatin F, immunosuppression, NK cells, N-Glycosylation |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 23.05.2023 |
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| Article acceptance date: | 06.11.2023 |
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| Publication date: | 13.12.2023 |
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| Publisher: | Springer Nature |
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| Year of publishing: | 2024 |
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| Number of pages: | 19 str. |
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| Numbering: | Vol. 81, iss. 1, art. 8 |
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| Source: | Švica |
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| PID: | 20.500.12556/DiRROS-23487  |
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| UDC: | 577.27:615.37 |
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| ISSN on article: | 1420-9071 |
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| DOI: | 10.1007/s00018-023-05041-x |
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| COBISS.SI-ID: | 177482499 |
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| Copyright: | © The Author(s) 2023 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 14.12. 2023;
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| Publication date in DiRROS: | 04.09.2025 |
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| Views: | 313 |
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| Downloads: | 91 |
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