Mateja Prunk (Author), Milica Perišić (Author), Tanja Jakoš (Author), Jerica Sabotič (Author), Urban Švajger (Author), Janko Kos (Author)

Abstract

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.

Keywords

cystatin F;cathepsins;cytotoxic lymphocytes;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 616.1
COBISS: 43955203 Link will open in a new window
ISSN: 2072-6694
Views: 156
Downloads: 44
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Other data

Secondary language: Slovenian
Secondary keywords: cistatin F;katepsini;citotoksični limfociti;
Type (COBISS): Article
Pages: str. 1-14
Volume: ǂVol. ǂ12
Issue: ǂiss. ǂ12
Chronology: Dec. 2020
DOI: 10.3390/cancers12123660
ID: 14452185