20.500.12556/DiRROS-23487 Different glycosylation profiles of cystatin F alter the cytotoxic potential of natural killer cells 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. cystatin F immunosuppression NK cells N-Glycosylation cistatin F imunosupresija naravne celice ubijalke naravne celice ubijalke - glikozilacija true false true Springer Nature Švica Angleški jezik Slovenski jezik © The Author(s) 2023 Neznano 2025-09-04 13:33:53 2025-09-04 13:33:53 2025-10-24 03:54:25 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 14.12. 2023; 19 str. iss. 1, art. 8 Vol. 81 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2023-05-23 2023-11-06 2023-12-13 577.27:615.37 1420-9071 10.1007/s00018-023-05041-x 177482499 RAZ_Senjor_Emanuela_2024.pdf RAZ_Senjor_Emanuela_2024.pdf 1 04686CF42F24E7542363D4B4ED34082F 463075db1991f5aaa1c9250ab9528a9f87920d181eaf9a35ce6962ca538d1244 23efc24e-8984-11f0-9bb7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=34738 Institut Jožef Stefan 0 0 0