prikaz prve stranice dokumenta Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora
Access restricted to students and staff of home institution
doctoral thesis
Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora
Rijeka: University of Rijeka, Faculty of Medicine, 2016. urn:nbn:hr:184:415973
Jelenčić, Vedrana
University of Rijeka
Faculty of Medicine
Department of Histology and Embryology

Institutional repository: Repository of the University of Rijeka, Faculty of Medicine

Cite this document

Jelenčić, V. (2016). Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora (Doctoral thesis). Rijeka: University of Rijeka, Faculty of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:184:415973

Jelenčić, Vedrana. "Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2016. https://urn.nsk.hr/urn:nbn:hr:184:415973

Jelenčić, Vedrana. "Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2016. https://urn.nsk.hr/urn:nbn:hr:184:415973

Jelenčić, V. (2016). 'Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora', Doctoral thesis, University of Rijeka, Faculty of Medicine, accessed 07 November 2024, https://urn.nsk.hr/urn:nbn:hr:184:415973

Jelenčić V. Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora [Doctoral thesis]. Rijeka: University of Rijeka, Faculty of Medicine; 2016 [cited 2024 November 07] Available at: https://urn.nsk.hr/urn:nbn:hr:184:415973

V. Jelenčić, "Mehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora", Doctoral thesis, University of Rijeka, Faculty of Medicine, Rijeka, 2016. Available at: https://urn.nsk.hr/urn:nbn:hr:184:415973

Metadata
TitleMehanizam nadzora tumora stanicama NK u miševa s nedostatkom NKG2D receptora
Title (english)NK cell-mediated tumor surveillance in NKG2D deficient mice
AuthorVedrana Jelenčić
MentorBojan Polić (mentor)
Committee memberGordana Laškarin (predsjednik povjerenstva)
Committee memberReno Hrašćan (član povjerenstva)
Committee memberAstrid Krmpotić (član povjerenstva)
Committee memberBojan Polić (član povjerenstva)
GranterUniversity of Rijeka
Faculty of Medicine
(Department of Histology and Embryology)
Rijeka
Defense date and country2016-10-19, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Cilj istraživanja: Naša prethodna istraživanja su pokazala da nedostatak NKG2D receptora dovodi do hiperreaktivnosti stanica NK. Glavni cilj ovog istraživanja bio je razjasniti molekularne mehanizme koji dovode do razvoja hiperreaktivnog fenotipa Klrk1-/- stanica NK te istražiti koje su posljedice iste na kontrolu tumora i na razvoj šećerne bolesti tipa 2. Materijal i metode: Kako bih istražila posljedice hiperreaktivnosti stanica NK na kontrolu tumora koristila sam model B16 melanoma i primarnog timoma. Za poticanje razvoja šećerne bolesti tipa 2 koristila sam masnu djetu. Funkcionalnim testovima i protočnom citometrijom analizirala sam funkcije stanica NK. U radu sam koristila genetski modificirane miševe kako bih ispitala ulogu određenih receptora i signalnih molekula in vivo i in vitro. Rezultati: Nedostatak izražaja NKG2D receptora rezultira specifičnom hiperreaktivnošću stanica NK preko NCR1 i CD16 aktivacijskih receptora. Opažena hiperreaktivnost posljedica je nedostatka signaliranja preko NKG2D-DAP12 signalne osi te korelira sa smanjenim izražajem CD3ζ i ZAP70 molekula. Posljedica opažene hiperreaktivnosti kod Klrk1-/- miševa je bolja kontrola tumora i MCMV infekcije, ali i povećana sklonost istih razvoju šećerne bolesti tipa 2. Zaključak: Rezultati ovog istraživanja po prvi puta pokazuju da jedan aktivacijski receptor regulira aktivnost drugog aktivacijskog receptora stanica NK, što ukazuje na dodatnu razinu regulacije izvršnih funkcija stanica NK. Rezultati ukazuju da rano tijekom razvoja stanica NK NKG2D /DAP12 signalna os utječe na postavljanje praga aktivacije za NCR1 i CD16 receptore. Gubitak ove regulacije dovodi do razvoja njihove hiperreaktivnosti koja imati svoje pozitivne, ali i negativne učinke.
Abstract (english)
Objectives: Our group has previously shown that NKG2D plays an important role in NK cell development. NKG2D-deficiency resulted in hyperreactive phenotype of NK cells which caused better control of MCMV infection. Main goals of this research were to investigate molecular mechanisms behind the observed hyperreactivity and how it influences tumor control and development of diabetes mellitus type 2. Materials and methods: To investigate how the hyperreactivity influences tumor control I used two tumor models: γ irradiation induced thymomas and B16 melanoma. To induce diabetes mellitus type 2 I used high-fat diet. Using different functional assays and flow cytometry I analyzed function of NK cells. Different genetically modified mice were used to investigate roles of specific receptors and signaling molecules. Results: NKG2D-deficiency results in specific hyperreactivity through NCR1 and CD16 receptors. This hyperreactivity is due to the lack of signaling through NKG2D-DAP12 and is correlated with reduced expression of CD3ζ and Zap70. The hyperreactivity results in better control of tumors and of MCMV infection by Klrk1-/- mice, whereas makes them more prone to diabetes. Conclusion: This research shows for the first time that an activating receptor can influence activity of another activating NK receptor, which indicates that there is another layer of NK cell regulation. It seems that in early stage of NK cell-development, NKG2D/DAP12 axis sets threshold for CD16 and NCR1. Loss of this regulation leads to the hyperreactivity which can have positive, but also negative outcomes.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:184:415973
ProjectNumber: 062-0621261-1271
Title: Uloga NKG2D u razvoju, homeostazi i efektorskim funkcijama imunološkog sustava
Title: The role of NKG2D in the development and effector functions of the immune system
Leader: Bojan Polić
Jurisdiction: Croatia
Funder: MZOS
Funding stream: ZP
ProjectNumber: HR.3.2.01-0263
Title: Mehanizmi prirođene imunosti u razvoju upale visceralnog masnog tkiva i rezistencije na inzulin u debljini
Leader: Bojan Polić
Jurisdiction: Croatia
Funder: EK
Funding stream: ESF
Study programmeTitle: Biomedicine Postgraduate (doctoral) study programme
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Created on2022-03-17 10:59:50