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Extracellular cystatin F is internalised by cytotoxic T lymphocytes and decreases their cytotoxicity
ID
Prunk, Mateja
(
Author
),
ID
Perišić, Milica
(
Author
),
ID
Jakoš, Tanja
(
Author
),
ID
Sabotič, Jerica
(
Author
),
ID
Švajger, Urban
(
Author
),
ID
Kos, Janko
(
Author
)
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https://www.mdpi.com/2072-6694/12/12/3660
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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.
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
Views:
1003
Downloads:
132
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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
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