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Vloga cistatina F v citotoksičnih limfocitih T, tretiranih z zaviralci imunskih kontrolnih točk = The role of cystatin F in cytotoxic T lymphocytes, treated with immune checkpoint inhibitors : enoviti magistrski študijski program FarmacijaPruš, MimaCistatin F spada v družino cistatinov tipa II, ki predstavljajo zaviralce cisteinskih peptidaz. Izraža se predvsem v imunskih celicah, kot so monociti, dendritične celice, naravne celice ubijalke in ... citotoksični limfociti T. Sintetizira se kot disulfidno vezan neaktivni dimer, ki se lahko izloča iz celic ali pa se prenese v endosome/lizosome. V endosomih/lizosomih se cistatin F aktivira z monomerizacijo, ki jo olajša proteolitična cepitev 15 aminokislin na njegovem N-koncu. Proteolitična cepitev spremeni inhibitorne lastnosti cistatina F, saj šele po cepitvi cistatin F postane močan zaviralec katepsina C. Neaktivni dimerni cistatin F, ki ga izločajo celice, lahko privzamejo okoliške celice in ga prenesejo v endosome/lizosome, kjer se aktivira. Povečano vsebnost cistatina F so odkrili v citotoksičnih limfocitih, kot so naravne celice ubijalke in citotoksični limfociti T, v katerih je njegovo povišano izražanje povezano z zmanjšano citotoksično funkcijo. Namen magistrske naloge je bil preučiti izražanje cistatina F v citotoksičnih limfocitih T, tretiranih z zaviralci imunskih kontrolnih točk. Za analizo vsebnosti cistatina F v celičnih linijah TALL-104, U937 in Jurkat smo uporabili pretočno citometrično analizo in prenos western. Celice TALL-104 smo aktivirali z uporabo proteinov CD3/CD28, konjugiranih z Dynabeads ali pa z ionomicinom v forbol 12-miristat 13-acetatu in po aktivaciji tretirali z zaviralci imunskih kontrolnih točk. Naše ugotovitve so pokazale, da je cistatin F dejansko prisoten v TALL-104, pri čemer se njegova ekspresija poveča ob celični aktivaciji. V aktiviranih celicah se je zmanjšalo izražanje katepsinov C in L ter izražanje in aktivnost grancimov in perforina. Tretiranje celic TALL-104 z zaviralci imunskih kontrolnih točk je znižalo raven cistatina F v aktiviranih celicah. Rezultati kažejo, da je cistatin F ključen regulator imunskega odziva v citotoksičnih celicah.Type of material - master's thesis ; adult, seriousPublication and manufacture - Ljubljana : [M. Pruš], 2023Language - slovenianCOBISS.SI-ID - 174712835
Author
Pruš, Mima
Other authors
Kos, Janko, 1959- |
Perišić, Milica
Topics
Citotoksičnost |
cistatin F |
cisteinski katepsini |
imunske kontrolne točke |
zaviralci imunskih kontrolnih točk
Library/institution |
City | Acronym | For loan | Other holdings |
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Faculty of Pharmacy, Ljubljana | Ljubljana | FFALJ |
reading room 1 cop.
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DRS, in which the journal is indexed
Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Pruš, Mima | |
Kos, Janko, 1959- | 04648 |
Perišić, Milica | 36596 |
Source: Personal bibliographies
and: SICRIS
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