Extracellular cystatin F is internalised by cytotoxic T lymphocytes and decreases their cytotoxicity

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

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.

• Jezik: Angleški jezik
• Ključne besede: cystatin F, cathepsins, cytotoxic lymphocytes, granzymes, perforin, TALL-104
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: 14 str.
• Številčenje: Vol. 12, iss. 12, art. 3660
• PID: 20.500.12556/RUL-134854
• UDK: 616.1
• ISSN pri članku: 2072-6694
• DOI: 10.3390/cancers12123660
• COBISS.SI-ID: 43955203
• Datum objave v RUL: 04.02.2022

Gradivo je del revije

• Naslov: Cancers
• Skrajšan naslov: Cancers
• Založnik: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 06.12.2020

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: cistatin F, katepsini, citotoksični limfociti

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: J4-1776
• Naslov: Izboljšanje imunoterapevtske vrednosti NK celic z modulacijo cistatina F

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P4-0127
• Naslov: Farmacevtska biotehnologija: znanost za zdravje