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Influence of aging on phenotypic and functional characteristics of dendritic cells from different rat strains

dc.contributor.advisorStojić-Vukanić, Zorica
dc.contributor.otherLeposavić, Gordana
dc.contributor.otherDimitrijević, Mirjana
dc.creatorBufan, Biljana S.
dc.date.accessioned2016-01-05T12:50:03Z
dc.date.available2016-01-05T12:50:03Z
dc.date.available2020-07-03T09:46:57Z
dc.date.issued2014-09-25
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=1853
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/3173
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:9522/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=46639119
dc.description.abstractDendritske ćelije (DĆ) su profesionalne antigen-prezentujuće ćelije koje čine sponu između urođenog i stečenog imuniteta i imaju važnu ulogu u imunskom odgovoru. Pored toga, DĆ imaju ulogu u uspostavljanju i održavanju imunološke tolerancije, kao i u patogenezi autoimunskih bolesti. Istraživanja na polju biologije starenja ćelija imunskog sistem su pokazala da tokom starenja komponente i urođenog i stečenog imuniteta podležu promenama. Podaci vezani za uticaj starenja na DĆ nisu konzistentni i uglavnom se odnose na ćelije humanog porekla, ćelije primata i miševa, dok nema podataka o uticaju starenja na DĆ pacova. Cilj ove doktorske disertacije je bio da se ispita uticaj starenja na fenotipske i funkcijske karakteristike konvencionalnih DĆ (kDĆ) pacova, kao i mogući značaj sojnih razlika za nastanak starenjem uslovljenih promena ovih ćelija. Takođe, cilj je bio i da se utvrdi da li starenjem uslovljene promene kDĆ pacova koreliraju sa promenom osetljivosti pacova na indukciju organ-specifičnih autoimunskih bolesti. Ispitivane su sveže izolovane kDĆ i stimulisane in vitro lipopolisaharidom (LPS). Konvencionalne DĆ su izolovane iz slezina pacova uzrasta 3 meseca (mladi odrasli pacovi) i 26 meseci (stari pacovi) Albino Oxford (AO) i Dark Agouti (DA) soja, koji pokazuju različit stepen osetljivosti na indukciju organ-specifične autoimunske bolesti posredovane Th1/Th17 limfocitima, kao što je eksperimentalni autoimunski encefalomijelitis (EAE). Starenje dovodi do veće zastupljenosti ćelija CD4- fenotipa u populaciji sveže izolovanih kDĆ starih AO pacova za razliku od mladih životinja, kod kojih je brojnija CD4+ subpopulacija, a ne utiče na zastupljenost ovih subpopulacija kod DA pacova, tako da je kod njih u oba uzrasta dominantna CD4- subpopulacija. Osim toga, sveže izolovane kDĆ starih AO pacova pokazuju nezreliji, a starih DA pacova zreliji fenotip, u odnosu na kDĆ mladih pacova odgovarajućeg soja, a što je procenjeno na osnovu nivoa ispoljenosti aktivacionih molekula (CD80, CD86 i CD40). U skladu sa fenotipom, endocitozni kapacitet kDĆ starih AO pacova je bio veći, dok je kod kDĆ starih DA pacova bio manji. Starenje dovodi do promena u ekspresiji iRNK za proinflamatorne i imunoregulatorne citokine kod pacova oba soja, s tim što su te promene suprotne kada je u pitanju iRNK za IL-6 i IL-1β (starenje smanjuje ekspresiju iRNK za IL-6, a povećava ekspresiju iRNK za IL-1β kod AO), različite (iRNK za IL-10 raste kod DA, a ne menja se kod AO pacova) ili slične (ekspresija TNF-a se povećava kod oba soja pacova, a iRNK za TGF-β se značajno ne menja)...sr
dc.description.abstractDendritic cells (DCs) are the professional antigen-presenting cells that form an interface between innate and adaptive immunity and play an important role in the immune response. They are also central in the establishment and maintenance of immune tolerance, as well as in the pathogenesis of autoimmune diseases. Aging is associated with the progressive immune system changes, which involve all types of immune cells. The data on age-associated DC alterations origin mainly from studies in mice and human, and are largely inconsistent, while there are no data on the influence of aging on rat DCs. The aim of this thesis was to elucidate the influence of aging on the phenotypic and functional characteristics of conventional DCs (cDCs), and the possible significance of strain differences in the development of age-related changes. In addition, this thesis was aimed to investigate a putative correlation between age-related changes in cDC biology and rat susceptibility to induction of organ-specific autoimmune diseases. Freshly isolated cDCs and cDCs stimulated in vitro with lipopolysaccharide (LPS) were investigated. The cells were isolated from the spleens of 3- (young adult) and 26 monthold (aged) rats of Albino Oxford (AO) and Dark Agouti (DA) strain, which are relatively resistant (AO) and susceptible (DA) to the induction of Th1/Th17-mediated organ-specific autoimmune disease, as it is experimental autoimmune encephalomyelitis (EAE). In AO rats aging increased relative proportion of cells exhibiting CD4- phenotype within population of freshly isolated cDCs, while in young animals CD4+ cells represented the predominant subpopulation within cDCs. In DA rats aging did not affect cDC subset composition, so predominance of CD4- subset within cDCs in rats of both ages was found. Aging affected surface phenotype and endocytic capacity of freshly isolated cDCs in a strain-specific manner. Namely, the lower surface density of activation markers (CD80, CD86 and CD40) on cDCs from aged AO rats and their higher endocytic capacity suggested that they were less mature that cDCs from young rats. To the contrary, increased surface expression of activation markers on cDCs and decreased endocytic capacity of these cells in aged DA rats suggested that they were more mature that corresponding cells from young rats...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Фармацеутски факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectkonvencionalne dendritske ćelije pacovasr
dc.subjectrat conventional dendritic cellsen
dc.subjectagingen
dc.subjectstrain differences in ratsen
dc.subjectTh polarizationen
dc.subjectallostimulatory capacityen
dc.subjectcytokine productionen
dc.subjectendocytic capacityen
dc.subjectexperimental autoimmune encephalomyelitisen
dc.subjectstarenjesr
dc.subjectsojne razlikesr
dc.subjectTh polarizacijasr
dc.subjectalostimulatorna sposobnostsr
dc.subjectendocitozna sposobnostsr
dc.subjecteksperimentalni autoimunski encefalomijelitissr
dc.titleUticaj starenja na fenotipske i funkcijske karakterisrtike dendritiskih ćelija različitih sojeva pacovasr
dc.titleInfluence of aging on phenotypic and functional characteristics of dendritic cells from different rat strainsen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dcterms.abstractСтојић-Вуканић, Зорица; Лепосавић, Гордана; Димитријевић, Мирјана; Буфан, Биљана С.; Утицај старења на фенотипске и функцијске карактерисртике дендритиских ћелија различитих сојева пацова; Утицај старења на фенотипске и функцијске карактерисртике дендритиских ћелија различитих сојева пацова;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/24015/Biljana_Bufan_referat_FF.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/24014/Disertacija.pdf


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