20.500.12556/RUL-134854 Extracellular cystatin F is internalised by cytotoxic T lymphocytes and decreases their cytotoxicity Cystatin F is a protein inhibitor of cysteine cathepsins, peptidases involved in the activation of the effector molecules of the perforin/granzyme pathway. Cystatin F was previously shown to regulate natural killer cell cytotoxicity. Here, we show that extracellular cystatin F has a role in regulating the killing efficiency of cytotoxic T lymphocytes (CTLs). Extracellular cystatin F was internalised into TALL-104 cells, a cytotoxic T cell line, and decreased their cathepsin C and H activity. Correspondingly, granzyme A and B activity was also decreased and, most importantly, the killing efficiency of TALL-104 cells as well as primary human CTLs was reduced. The N-terminally truncated form of cystatin F, which can directly inhibit cathepsin C (unlike the full-length form), was more effective than the full-length inhibitor. Furthermore, cystatin F decreased cathepsin L activity, which, however, did not affect perforin processing. Cystatin F derived from K-562 target cells could also decrease the cytotoxicity of TALL-104 cells. These results clearly show that, by inhibiting cysteine cathepsin proteolytic activity, extracellular cystatin F can decrease the cytotoxicity of CTLs and thus compromise their function. cystatin F cathepsins cytotoxic lymphocytes granzymes perforin TALL-104 cistatin F katepsini citotoksični limfociti true false true Angleški jezik Slovenski jezik Članek v reviji 2022-02-04 12:59:12 2022-02-04 12:59:16 2022-09-14 04:10:20 0000-00-00 00:00:00 2020 0 0 14 str. iss. 12, art. 3660 Vol. 12 Dec. 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.1 2072-6694 10.3390/cancers12123660 43955203 RAZ_Prunk_Mateja_2020.pdf RAZ_Prunk_Mateja_2020.pdf 1 B5FCEA90FFA7037B47AD076461BC3B0C e8e45140e32088d917244c4dcdbf6b7671d4c7c91b4b131d1c2c7678ad3e90ae 0ca0ca00-85b2-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153555 https://www.mdpi.com/2072-6694/12/12/3660 1 a82ce54e-85b1-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153554 Fakulteta za farmacijo 0 0 0