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

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

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.

• Language: English
• Keywords: cystatin F, cathepsins, cytotoxic lymphocytes, granzymes, perforin, TALL-104
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 14 str.
• Numbering: Vol. 12, iss. 12, art. 3660
• PID: 20.500.12556/RUL-134854
• UDC: 616.1
• ISSN on article: 2072-6694
• DOI: 10.3390/cancers12123660
• COBISS.SI-ID: 43955203
• Publication date in RUL: 04.02.2022

Record is a part of a journal

• Title: Cancers
• Shortened title: Cancers
• Publisher: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 06.12.2020

Secondary language

• Language: Slovenian
• Keywords: cistatin F, katepsini, citotoksični limfociti

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J4-1776
• Name: Izboljšanje imunoterapevtske vrednosti NK celic z modulacijo cistatina F

• Funder: ARRS - Slovenian Research Agency
• Project number: P4-0127
• Name: Farmacevtska biotehnologija: znanost za zdravje