TY  - JOUR
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Dinić, Miroslav
AU  - Bisenić, Aleksandar
AU  - Golić, Nataša
AU  - Vucević, Dragana
AU  - Đokić, Jelena
AU  - Tomić, Sergej
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1540
AB  - Over-activated myeloid cells and disturbance in gut microbiota composition are critical factors contributing to the pathogenesis of Multiple Sclerosis (MS). Myeloid-derived suppressor cells (MDSCs) emerged as promising regulators of chronic inflammatory diseases, including autoimmune diseases. However, it remained unclear whether MDSCs display any therapeutic potential in MS, and how this therapy modulates gut microbiota composition. Here, we assessed the potential of in vitro generated bone marrow-derived MDSCs to ameliorate experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats and investigated how their application associates with the changes in gut microbiota composition. MDSCs differentiated with prostaglandin (PG)E2 (MDSC-PGE2) and control MDSCs (differentiated without PGE2) displayed strong immunosuppressive properties in vitro, but only MDSC-PGE2 significantly ameliorated EAE symptoms. This effect correlated with a reduced infiltration of Th17 and IFN-gamma-producing NK cells, and an increased proportion of regulatory T cells in the CNS and spleen. Importantly, both MDSCs and MDSC-PGE2 prevented EAE-induced reduction of gut microbiota diversity, but only MDSC-PGE2 prevented the extensive alterations in gut microbiota composition following their early migration into Payer's patches and mesenteric lymph nodes. This phenomenon was related to the significant enrichment of gut microbial taxa with potential immunoregulatory properties, as well as higher levels of butyrate, propionate, and putrescine in feces. This study provides new insights into the host-microbiota interactions in EAE, suggesting that activated MDSCs could be potentially used as an efficient therapy for acute phases of MS. Considering a significant association between the efficacy of MDSC-PGE2 and gut microbiota composition, our findings also provide a rationale for further exploring the specific microbial metabolites in MS therapy.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Gut Microbes
T1  - Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis
IS  - 1
VL  - 14
DO  - 10.1080/19490976.2022.2127455
ER  - 

@article{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Dinić, Miroslav and Bisenić, Aleksandar and Golić, Nataša and Vucević, Dragana and Đokić, Jelena and Tomić, Sergej",
year = "2022",
abstract = "Over-activated myeloid cells and disturbance in gut microbiota composition are critical factors contributing to the pathogenesis of Multiple Sclerosis (MS). Myeloid-derived suppressor cells (MDSCs) emerged as promising regulators of chronic inflammatory diseases, including autoimmune diseases. However, it remained unclear whether MDSCs display any therapeutic potential in MS, and how this therapy modulates gut microbiota composition. Here, we assessed the potential of in vitro generated bone marrow-derived MDSCs to ameliorate experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats and investigated how their application associates with the changes in gut microbiota composition. MDSCs differentiated with prostaglandin (PG)E2 (MDSC-PGE2) and control MDSCs (differentiated without PGE2) displayed strong immunosuppressive properties in vitro, but only MDSC-PGE2 significantly ameliorated EAE symptoms. This effect correlated with a reduced infiltration of Th17 and IFN-gamma-producing NK cells, and an increased proportion of regulatory T cells in the CNS and spleen. Importantly, both MDSCs and MDSC-PGE2 prevented EAE-induced reduction of gut microbiota diversity, but only MDSC-PGE2 prevented the extensive alterations in gut microbiota composition following their early migration into Payer's patches and mesenteric lymph nodes. This phenomenon was related to the significant enrichment of gut microbial taxa with potential immunoregulatory properties, as well as higher levels of butyrate, propionate, and putrescine in feces. This study provides new insights into the host-microbiota interactions in EAE, suggesting that activated MDSCs could be potentially used as an efficient therapy for acute phases of MS. Considering a significant association between the efficacy of MDSC-PGE2 and gut microbiota composition, our findings also provide a rationale for further exploring the specific microbial metabolites in MS therapy.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Gut Microbes",
title = "Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis",
number = "1",
volume = "14",
doi = "10.1080/19490976.2022.2127455"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Dinić, M., Bisenić, A., Golić, N., Vucević, D., Đokić, J.,& Tomić, S.. (2022). Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis. in Gut Microbes
Taylor & Francis Inc, Philadelphia., 14(1).
https://doi.org/10.1080/19490976.2022.2127455

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Dinić M, Bisenić A, Golić N, Vucević D, Đokić J, Tomić S. Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis. in Gut Microbes. 2022;14(1).
doi:10.1080/19490976.2022.2127455 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Dinić, Miroslav, Bisenić, Aleksandar, Golić, Nataša, Vucević, Dragana, Đokić, Jelena, Tomić, Sergej, "Myeloid-derived suppressor cells prevent disruption of the gut barrier, preserve microbiota composition, and potentiate immunoregulatory pathways in a rat model of experimental autoimmune encephalomyelitis" in Gut Microbes, 14, no. 1 (2022),
https://doi.org/10.1080/19490976.2022.2127455 . .

TY  - JOUR
AU  - Radojević, Dušan
AU  - Tomić, Sergej
AU  - Mihajlović, Dusan
AU  - Tolinački, Maja
AU  - Pavlović, Bojan
AU  - Vucević, Dragana
AU  - Bojić, Svetlana
AU  - Golić, Nataša
AU  - Čolić, Miodrag
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1475
AB  - Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher alpha-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-alpha, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-alpha, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Gut Microbes
T1  - Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro
IS  - 1
VL  - 13
DO  - 10.1080/19490976.2021.1921927
ER  - 

@article{
author = "Radojević, Dušan and Tomić, Sergej and Mihajlović, Dusan and Tolinački, Maja and Pavlović, Bojan and Vucević, Dragana and Bojić, Svetlana and Golić, Nataša and Čolić, Miodrag and Đokić, Jelena",
year = "2021",
abstract = "Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher alpha-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-alpha, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFN gamma, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower alpha-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-alpha, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Gut Microbes",
title = "Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro",
number = "1",
volume = "13",
doi = "10.1080/19490976.2021.1921927"
}

Radojević, D., Tomić, S., Mihajlović, D., Tolinački, M., Pavlović, B., Vucević, D., Bojić, S., Golić, N., Čolić, M.,& Đokić, J.. (2021). Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes
Taylor & Francis Inc, Philadelphia., 13(1).
https://doi.org/10.1080/19490976.2021.1921927

Radojević D, Tomić S, Mihajlović D, Tolinački M, Pavlović B, Vucević D, Bojić S, Golić N, Čolić M, Đokić J. Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro. in Gut Microbes. 2021;13(1).
doi:10.1080/19490976.2021.1921927 .

Radojević, Dušan, Tomić, Sergej, Mihajlović, Dusan, Tolinački, Maja, Pavlović, Bojan, Vucević, Dragana, Bojić, Svetlana, Golić, Nataša, Čolić, Miodrag, Đokić, Jelena, "Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro" in Gut Microbes, 13, no. 1 (2021),
https://doi.org/10.1080/19490976.2021.1921927 . .

TY  - CONF
AU  - Bekić, Marina
AU  - Dinić, Miroslav
AU  - Radojević, Dušan
AU  - Ilić, Nataša
AU  - Vucević, Dragana
AU  - Vasilev, Sasa
AU  - Đokić, Jelena
AU  - Tomić, Sergej
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1436
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro
EP  - 179
SP  - 179
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1436
ER  - 

@conference{
author = "Bekić, Marina and Dinić, Miroslav and Radojević, Dušan and Ilić, Nataša and Vucević, Dragana and Vasilev, Sasa and Đokić, Jelena and Tomić, Sergej",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro",
pages = "179-179",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1436"
}

Bekić, M., Dinić, M., Radojević, D., Ilić, N., Vucević, D., Vasilev, S., Đokić, J.,& Tomić, S.. (2021). Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro. in European Journal of Immunology
Wiley, Hoboken., 51, 179-179.
https://hdl.handle.net/21.15107/rcub_imagine_1436

Bekić M, Dinić M, Radojević D, Ilić N, Vucević D, Vasilev S, Đokić J, Tomić S. Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro. in European Journal of Immunology. 2021;51:179-179.
https://hdl.handle.net/21.15107/rcub_imagine_1436 .

Bekić, Marina, Dinić, Miroslav, Radojević, Dušan, Ilić, Nataša, Vucević, Dragana, Vasilev, Sasa, Đokić, Jelena, Tomić, Sergej, "Prostaglandin E2 differentially regulate the suppressive mechanisms in myeloid derived suppressor cells subsets in vitro" in European Journal of Immunology, 51 (2021):179-179,
https://hdl.handle.net/21.15107/rcub_imagine_1436 .

TY  - CONF
AU  - Radojević, Dušan
AU  - Tomić, Sergej
AU  - Mihajlović, Dusan
AU  - Tolinački, Maja
AU  - Pavlović, Bojan
AU  - Vucević, Dragana
AU  - Bojić, Svetlana
AU  - Golić, Nataša
AU  - Čolić, Miodrag
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1437
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition
EP  - 32
SP  - 32
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1437
ER  - 

@conference{
author = "Radojević, Dušan and Tomić, Sergej and Mihajlović, Dusan and Tolinački, Maja and Pavlović, Bojan and Vucević, Dragana and Bojić, Svetlana and Golić, Nataša and Čolić, Miodrag and Đokić, Jelena",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition",
pages = "32-32",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1437"
}

Radojević, D., Tomić, S., Mihajlović, D., Tolinački, M., Pavlović, B., Vucević, D., Bojić, S., Golić, N., Čolić, M.,& Đokić, J.. (2021). Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition. in European Journal of Immunology
Wiley, Hoboken., 51, 32-32.
https://hdl.handle.net/21.15107/rcub_imagine_1437

Radojević D, Tomić S, Mihajlović D, Tolinački M, Pavlović B, Vucević D, Bojić S, Golić N, Čolić M, Đokić J. Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition. in European Journal of Immunology. 2021;51:32-32.
https://hdl.handle.net/21.15107/rcub_imagine_1437 .

Radojević, Dušan, Tomić, Sergej, Mihajlović, Dusan, Tolinački, Maja, Pavlović, Bojan, Vucević, Dragana, Bojić, Svetlana, Golić, Nataša, Čolić, Miodrag, Đokić, Jelena, "Inter-donor variability in dendritic cells capacity to respond to stimulation in vitro associates with donors gut microbiota composition" in European Journal of Immunology, 51 (2021):32-32,
https://hdl.handle.net/21.15107/rcub_imagine_1437 .

TY  - JOUR
AU  - Marković, Milan
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Mihajlović, Dusan
AU  - Vucević, Dragana
AU  - Gazivoda, Dragan
AU  - Duka, Milos
AU  - Čolić, Miodrag
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1104
AB  - Background/Aim. Mesenchymal stem cells (MSCs) have been shown to suppress immune and inflammatory reactions. However, it is not known whether MSCs from inflammatory tissues, such as periapical lesions (PLs) have similar effects. This question was addressed in this study in which the aim was to examine the capacity of PL-MSCs for modulating cytokine production by local immune cells. Methods. PL-MSCs were isolated from asymptomatic (as) and symptomatic (sy) PLs. Their phenotype was analyzed by flow cytometry by detecting MSC surface markers. Anti-inflammatory and immunomodulatory properties of PL-MSCs were examined by measuring cytokine production in direct co-culture experiments with mononuclear cells (MNCs) isolated from asPLs and syPLs, respectively. The levels of cytokines in supernatants were determined by specific ELISA kits. Results. Both PL-MSCs lines were characterized by typical MSC phenotype, with the predominance of CD29, CD44, CD90, CD105 and CD166. However, the lines, independently of their similar phenotype had the same modulatory effect on cytokine production, but the response of asPL-MNCs and syPL-MNCs was different, in spite of similar composition of these MNCs. Both MSC lines inhibited the production of inflammatory cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor-0 (TNF-0). However, IL-8 was only down-regulated in the co-culture of these MSC lines with syPL-MNCs. The PL-MSCs also modulated the production of immunoregulatory cytokines. Transforming growth factor-0 (TGF-0) was up-regulated by both as- and syPL-MNCs but IL-10 was up-regulated only by asPL-MNCs. Conclusion. Our results showed that PL-MSCs contribute to the restriction of local inflammatory and immune responses, but this effect is probably less efficient during the exacerbation of PL inflammation.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells
EP  - 480
IS  - 5
SP  - 473
VL  - 75
DO  - 10.2298/VSP160901272M
ER  - 

@article{
author = "Marković, Milan and Tomić, Sergej and Đokić, Jelena and Mihajlović, Dusan and Vucević, Dragana and Gazivoda, Dragan and Duka, Milos and Čolić, Miodrag",
year = "2018",
abstract = "Background/Aim. Mesenchymal stem cells (MSCs) have been shown to suppress immune and inflammatory reactions. However, it is not known whether MSCs from inflammatory tissues, such as periapical lesions (PLs) have similar effects. This question was addressed in this study in which the aim was to examine the capacity of PL-MSCs for modulating cytokine production by local immune cells. Methods. PL-MSCs were isolated from asymptomatic (as) and symptomatic (sy) PLs. Their phenotype was analyzed by flow cytometry by detecting MSC surface markers. Anti-inflammatory and immunomodulatory properties of PL-MSCs were examined by measuring cytokine production in direct co-culture experiments with mononuclear cells (MNCs) isolated from asPLs and syPLs, respectively. The levels of cytokines in supernatants were determined by specific ELISA kits. Results. Both PL-MSCs lines were characterized by typical MSC phenotype, with the predominance of CD29, CD44, CD90, CD105 and CD166. However, the lines, independently of their similar phenotype had the same modulatory effect on cytokine production, but the response of asPL-MNCs and syPL-MNCs was different, in spite of similar composition of these MNCs. Both MSC lines inhibited the production of inflammatory cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor-0 (TNF-0). However, IL-8 was only down-regulated in the co-culture of these MSC lines with syPL-MNCs. The PL-MSCs also modulated the production of immunoregulatory cytokines. Transforming growth factor-0 (TGF-0) was up-regulated by both as- and syPL-MNCs but IL-10 was up-regulated only by asPL-MNCs. Conclusion. Our results showed that PL-MSCs contribute to the restriction of local inflammatory and immune responses, but this effect is probably less efficient during the exacerbation of PL inflammation.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells",
pages = "480-473",
number = "5",
volume = "75",
doi = "10.2298/VSP160901272M"
}

Marković, M., Tomić, S., Đokić, J., Mihajlović, D., Vucević, D., Gazivoda, D., Duka, M.,& Čolić, M.. (2018). Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 75(5), 473-480.
https://doi.org/10.2298/VSP160901272M

Marković M, Tomić S, Đokić J, Mihajlović D, Vucević D, Gazivoda D, Duka M, Čolić M. Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells. in Vojnosanitetski pregled. 2018;75(5):473-480.
doi:10.2298/VSP160901272M .

Marković, Milan, Tomić, Sergej, Đokić, Jelena, Mihajlović, Dusan, Vucević, Dragana, Gazivoda, Dragan, Duka, Milos, Čolić, Miodrag, "Mesenchymal stem cells from periapical lesions modulate cytokine production by local immune cells" in Vojnosanitetski pregled, 75, no. 5 (2018):473-480,
https://doi.org/10.2298/VSP160901272M . .

TY  - JOUR
AU  - Pavlović, Bojan
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Vasilijić, Sasa
AU  - Vucević, Dragana
AU  - Lukić, Jovanka
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Marković, Milan
AU  - Čolić, Miodrag
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/846
AB  - Background aims. Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited. Methods. We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise. Results. Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD 14, low expression of CD la and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1 beta and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-beta production by fDC-primed CD3(+)T cells and their stronger antiproliferative capacity. Conclusions. We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.
PB  - Elsevier Sci Ltd, Oxford
T2  - Cytotherapy
T1  - Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties
EP  - 1776
IS  - 12
SP  - 1763
VL  - 17
DO  - 10.1016/j.jcyt.2015.08.001
ER  - 

@article{
author = "Pavlović, Bojan and Tomić, Sergej and Đokić, Jelena and Vasilijić, Sasa and Vucević, Dragana and Lukić, Jovanka and Gruden-Movsesijan, Alisa and Ilić, Nataša and Marković, Milan and Čolić, Miodrag",
year = "2015",
abstract = "Background aims. Because of the labor-intensive and time-consuming conventional protocols for the generation of dendritic cells (DCs) as the most promising tools for anti-cancer therapy that enable the induction of a T-helper (Th)1-mediated anti-tumor immune response, the use of short-term protocols has been proposed. However, data on the applicability of such protocols in cancer immunotherapy are quite limited. Methods. We compared the phenotypic and functional capability of fast DCs (fDCs) differentiated for 24 h and then matured for 48 h with Poly (I:C), a strong Th1-promoting agent, with donor-matched conventional DCs (cDCs) differentiated for 5 days and matured likewise. Results. Of 12 donors tested, we identified seven whose monocytes failed to develop into immunogenic DCs through the use of fDC protocol, on the basis of incomplete downregulation of CD 14, low expression of CD la and macrophage-like morphology. Such fDCs have significantly lower expression of CD83, CD86, CCR7 and CD40, weaker allo-stimulatory Th1- and Th17-polarizing capacity caused by poor production of interleukin (IL)-12p70 and IL-23 and high production of IL-10, and prominent Th2-polarizing capacity, compared with donor-matched cDCs. Furthermore, such fDCs had tolerogenic properties as judged by higher expression of indolamine dioxigenase-3, IDO-1 and IL-1 beta and induction of a higher percentage of CD4(+)CD25(+)FoxP3(+) T cells. These findings correlated with increased transforming growth factor (TGF)-beta production by fDC-primed CD3(+)T cells and their stronger antiproliferative capacity. Conclusions. We emphasize that although fDCs could probably be applied as an alternative to cDCs for cancer therapy, the fDC protocol should not be applied to donors whose DCs acquire tolerogenic capabilities.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Cytotherapy",
title = "Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties",
pages = "1776-1763",
number = "12",
volume = "17",
doi = "10.1016/j.jcyt.2015.08.001"
}

Pavlović, B., Tomić, S., Đokić, J., Vasilijić, S., Vucević, D., Lukić, J., Gruden-Movsesijan, A., Ilić, N., Marković, M.,& Čolić, M.. (2015). Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties. in Cytotherapy
Elsevier Sci Ltd, Oxford., 17(12), 1763-1776.
https://doi.org/10.1016/j.jcyt.2015.08.001

Pavlović B, Tomić S, Đokić J, Vasilijić S, Vucević D, Lukić J, Gruden-Movsesijan A, Ilić N, Marković M, Čolić M. Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties. in Cytotherapy. 2015;17(12):1763-1776.
doi:10.1016/j.jcyt.2015.08.001 .

Pavlović, Bojan, Tomić, Sergej, Đokić, Jelena, Vasilijić, Sasa, Vucević, Dragana, Lukić, Jovanka, Gruden-Movsesijan, Alisa, Ilić, Nataša, Marković, Milan, Čolić, Miodrag, "Fast dendritic cells matured with Poly (I:C) may acquire tolerogenic properties" in Cytotherapy, 17, no. 12 (2015):1763-1776,
https://doi.org/10.1016/j.jcyt.2015.08.001 . .

TY  - JOUR
AU  - Rajković, Ivan
AU  - Dragicević, Ana
AU  - Vasilijić, Sasa
AU  - Bozić, Biljana
AU  - Dzopalić, Tanja
AU  - Tomić, Sergej
AU  - Majstorović, Ivana
AU  - Vucević, Dragana
AU  - Đokić, Jelena
AU  - Balint, Bela
AU  - Čolić, Miodrag
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/477
AB  - P gt Langerhans' cells (LCs) represent a specific subset of dendritic cells (DCs) which are important for detecting and processing pathogens that penetrate the skin and epithelial barriers. The aim of our study was to explain what makes their in vitro counterparts - monocyte-derived Langerhans'-like cells (MoLCs) - unique compared with monocyte-derived dendritic cells (MoDCs). Immature MoDCs were generated by incubating peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. The addition of transforming growth factor-beta (TGF-beta) to this cytokine cocktail resulted in the generation of MoLCs. MoLCs showed a lower expression of CD83, CD86, HLA-DR and CCR7 compared with MoDCs, regardless of their maturational status. Both immature and mature MoLCs secreted higher quantities of IL-23 compared with MoDCs and this finding correlated with a higher secretion of IL-17 in co-culture of MoLCs with allogeneic CD4(+) T cells. Mature MoLCs, which produced higher levels of IL-12 and lower levels of IL-10 compared with mature MoDCs, were more potent at inducing interferon-gamma (IFN-gamma) production by CD4(+) T cells in the co-culture system. In conclusion, the finding that mature MoLCs stimulate stronger T-helper 1 and T-helper 17 immune responses than mature MoDCs, makes them better candidates for use in the preparation of anti-tumour DC vaccines.
PB  - Wiley, Hoboken
T2  - Immunology
T1  - Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells
EP  - 225
IS  - 2
SP  - 217
VL  - 132
DO  - 10.1111/j.1365-2567.2010.03356.x
ER  - 

@article{
author = "Rajković, Ivan and Dragicević, Ana and Vasilijić, Sasa and Bozić, Biljana and Dzopalić, Tanja and Tomić, Sergej and Majstorović, Ivana and Vucević, Dragana and Đokić, Jelena and Balint, Bela and Čolić, Miodrag",
year = "2011",
abstract = "P gt Langerhans' cells (LCs) represent a specific subset of dendritic cells (DCs) which are important for detecting and processing pathogens that penetrate the skin and epithelial barriers. The aim of our study was to explain what makes their in vitro counterparts - monocyte-derived Langerhans'-like cells (MoLCs) - unique compared with monocyte-derived dendritic cells (MoDCs). Immature MoDCs were generated by incubating peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4. The addition of transforming growth factor-beta (TGF-beta) to this cytokine cocktail resulted in the generation of MoLCs. MoLCs showed a lower expression of CD83, CD86, HLA-DR and CCR7 compared with MoDCs, regardless of their maturational status. Both immature and mature MoLCs secreted higher quantities of IL-23 compared with MoDCs and this finding correlated with a higher secretion of IL-17 in co-culture of MoLCs with allogeneic CD4(+) T cells. Mature MoLCs, which produced higher levels of IL-12 and lower levels of IL-10 compared with mature MoDCs, were more potent at inducing interferon-gamma (IFN-gamma) production by CD4(+) T cells in the co-culture system. In conclusion, the finding that mature MoLCs stimulate stronger T-helper 1 and T-helper 17 immune responses than mature MoDCs, makes them better candidates for use in the preparation of anti-tumour DC vaccines.",
publisher = "Wiley, Hoboken",
journal = "Immunology",
title = "Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells",
pages = "225-217",
number = "2",
volume = "132",
doi = "10.1111/j.1365-2567.2010.03356.x"
}

Rajković, I., Dragicević, A., Vasilijić, S., Bozić, B., Dzopalić, T., Tomić, S., Majstorović, I., Vucević, D., Đokić, J., Balint, B.,& Čolić, M.. (2011). Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells. in Immunology
Wiley, Hoboken., 132(2), 217-225.
https://doi.org/10.1111/j.1365-2567.2010.03356.x

Rajković I, Dragicević A, Vasilijić S, Bozić B, Dzopalić T, Tomić S, Majstorović I, Vucević D, Đokić J, Balint B, Čolić M. Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells. in Immunology. 2011;132(2):217-225.
doi:10.1111/j.1365-2567.2010.03356.x .

Rajković, Ivan, Dragicević, Ana, Vasilijić, Sasa, Bozić, Biljana, Dzopalić, Tanja, Tomić, Sergej, Majstorović, Ivana, Vucević, Dragana, Đokić, Jelena, Balint, Bela, Čolić, Miodrag, "Differences in T-helper polarizing capability between human monocyte-derived dendritic cells and monocyte-derived Langerhans'-like cells" in Immunology, 132, no. 2 (2011):217-225,
https://doi.org/10.1111/j.1365-2567.2010.03356.x . .

TY  - JOUR
AU  - Dzopalić, Tanja
AU  - Vucević, Dragana
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Chinou, Ioanna
AU  - Čolić, Miodrag
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/482
AB  - Different pharmacologically active components have been isolated from royal jelly. Some of them possess imunomodulatory activity, but the mechanisms of their effect on the immune system have not been elucidated yet. In this study we tested the effect of 3,10-dihydroxy-decanoic acid (3,10-DDA), a fatty acid isolated from royal jelly, on maturation and functions of human monocyte-derived dendritic cells (MoDCs). We showed that 3,10-DDA stimulated maturation of MoDCs by up-regulating the expression of CD40, CD54, CD86 and CD1a, and increased their allostimulatory potential in co-culture with allogeneic CD4(+)T cells. 3,10-DDA-treated MoDCs enhanced the production of IL-12 and IL-18, and stimulated the production of interferon-gamma in co-culture with allogeneic CD4(+)T cells, compared to control MoDCs. In contrast, the production of IL-10 was down-regulated. In conclusion, our results suggest that 3,10-DDA stimulates maturation and Th1 polarising capability of human MoDCs in vitro, which could be beneficial for anti-tumour and anti-viral immune responses.
PB  - Elsevier Sci Ltd, Oxford
T2  - Food Chemistry
T1  - 3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells
EP  - 1217
IS  - 3
SP  - 1211
VL  - 126
DO  - 10.1016/j.foodchem.2010.12.004
ER  - 

@article{
author = "Dzopalić, Tanja and Vucević, Dragana and Tomić, Sergej and Đokić, Jelena and Chinou, Ioanna and Čolić, Miodrag",
year = "2011",
abstract = "Different pharmacologically active components have been isolated from royal jelly. Some of them possess imunomodulatory activity, but the mechanisms of their effect on the immune system have not been elucidated yet. In this study we tested the effect of 3,10-dihydroxy-decanoic acid (3,10-DDA), a fatty acid isolated from royal jelly, on maturation and functions of human monocyte-derived dendritic cells (MoDCs). We showed that 3,10-DDA stimulated maturation of MoDCs by up-regulating the expression of CD40, CD54, CD86 and CD1a, and increased their allostimulatory potential in co-culture with allogeneic CD4(+)T cells. 3,10-DDA-treated MoDCs enhanced the production of IL-12 and IL-18, and stimulated the production of interferon-gamma in co-culture with allogeneic CD4(+)T cells, compared to control MoDCs. In contrast, the production of IL-10 was down-regulated. In conclusion, our results suggest that 3,10-DDA stimulates maturation and Th1 polarising capability of human MoDCs in vitro, which could be beneficial for anti-tumour and anti-viral immune responses.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Food Chemistry",
title = "3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells",
pages = "1217-1211",
number = "3",
volume = "126",
doi = "10.1016/j.foodchem.2010.12.004"
}

Dzopalić, T., Vucević, D., Tomić, S., Đokić, J., Chinou, I.,& Čolić, M.. (2011). 3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells. in Food Chemistry
Elsevier Sci Ltd, Oxford., 126(3), 1211-1217.
https://doi.org/10.1016/j.foodchem.2010.12.004

Dzopalić T, Vucević D, Tomić S, Đokić J, Chinou I, Čolić M. 3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells. in Food Chemistry. 2011;126(3):1211-1217.
doi:10.1016/j.foodchem.2010.12.004 .

Dzopalić, Tanja, Vucević, Dragana, Tomić, Sergej, Đokić, Jelena, Chinou, Ioanna, Čolić, Miodrag, "3,10-Dihydroxy-decanoic acid, isolated from royal jelly, stimulates Th1 polarising capability of human monocyte-derived dendritic cells" in Food Chemistry, 126, no. 3 (2011):1211-1217,
https://doi.org/10.1016/j.foodchem.2010.12.004 . .

TY  - JOUR
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Vasilijić, Sasa
AU  - Vucević, Dragana
AU  - Todorović, Vera
AU  - Supić, Gordana
AU  - Čolić, Miodrag
PY  - 2011
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/529
AB  - Adult mesenchymal stem cells (MSCs) have recently become a potent tool in regenerative medicine. Due to certain shortcomings of obtaining bone marrow MSCs, alternate sources of MSCs have been sought. In this work, we studied MSCs from dental pulp (DP-MSCs) and dental follicle (DF-MSCs), isolated from the same tooth/donor, to define differences in their phenotypic properties, differentiation potential, and immunomodulatory activities. Both cell types showed colony-forming ability and expressed typical MSCs markers, but differed in the levels of their expression. DF-MSCs proliferated faster, contained cells larger in diameter, exhibited a higher potential to form adipocytes and a lower potential to form chondrocytes and osteoblasts, compared with DP-MSCs. In contrast to DF-MSCs, DP-MSCs produced the transforming growth factor (TGF)-beta and suppressed proliferation of peripheral blood mononuclear cells, which could be neutralized with anti-TGF-beta antibody. The treatment with toll-like receptor 3 (TLR3) agonist augmented the suppressive potential of both cell types and potentiated TGF-beta and interleukin-6 secretions by these cells. TLR4 agonist augmented the suppressive potential of DF-MSCs and increased TGF-beta production, but abrogated the immunosuppressive activity of DP-MSCs by inhibiting TGF-beta production and the expression of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher expression of TLR3 and TLR4 by DP-MSCs compared with DF-MSCs. When transplanted in imunocompetent xenogenic host, both cell types induced formation of granulomatous tissue. In conclusion, our results suggest that dental MSCs are functionally different and each of these functions should be further explored in vivo before their specific biomedical applications.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Stem Cells and Development
T1  - Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists
EP  - 708
IS  - 4
SP  - 695
VL  - 20
DO  - 10.1089/scd.2010.0145
ER  - 

@article{
author = "Tomić, Sergej and Đokić, Jelena and Vasilijić, Sasa and Vucević, Dragana and Todorović, Vera and Supić, Gordana and Čolić, Miodrag",
year = "2011",
abstract = "Adult mesenchymal stem cells (MSCs) have recently become a potent tool in regenerative medicine. Due to certain shortcomings of obtaining bone marrow MSCs, alternate sources of MSCs have been sought. In this work, we studied MSCs from dental pulp (DP-MSCs) and dental follicle (DF-MSCs), isolated from the same tooth/donor, to define differences in their phenotypic properties, differentiation potential, and immunomodulatory activities. Both cell types showed colony-forming ability and expressed typical MSCs markers, but differed in the levels of their expression. DF-MSCs proliferated faster, contained cells larger in diameter, exhibited a higher potential to form adipocytes and a lower potential to form chondrocytes and osteoblasts, compared with DP-MSCs. In contrast to DF-MSCs, DP-MSCs produced the transforming growth factor (TGF)-beta and suppressed proliferation of peripheral blood mononuclear cells, which could be neutralized with anti-TGF-beta antibody. The treatment with toll-like receptor 3 (TLR3) agonist augmented the suppressive potential of both cell types and potentiated TGF-beta and interleukin-6 secretions by these cells. TLR4 agonist augmented the suppressive potential of DF-MSCs and increased TGF-beta production, but abrogated the immunosuppressive activity of DP-MSCs by inhibiting TGF-beta production and the expression of indolamine-2,3-dioxygenase-1. Some of these effects correlated with the higher expression of TLR3 and TLR4 by DP-MSCs compared with DF-MSCs. When transplanted in imunocompetent xenogenic host, both cell types induced formation of granulomatous tissue. In conclusion, our results suggest that dental MSCs are functionally different and each of these functions should be further explored in vivo before their specific biomedical applications.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Stem Cells and Development",
title = "Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists",
pages = "708-695",
number = "4",
volume = "20",
doi = "10.1089/scd.2010.0145"
}

Tomić, S., Đokić, J., Vasilijić, S., Vucević, D., Todorović, V., Supić, G.,& Čolić, M.. (2011). Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists. in Stem Cells and Development
Mary Ann Liebert, Inc, New Rochelle., 20(4), 695-708.
https://doi.org/10.1089/scd.2010.0145

Tomić S, Đokić J, Vasilijić S, Vucević D, Todorović V, Supić G, Čolić M. Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists. in Stem Cells and Development. 2011;20(4):695-708.
doi:10.1089/scd.2010.0145 .

Tomić, Sergej, Đokić, Jelena, Vasilijić, Sasa, Vucević, Dragana, Todorović, Vera, Supić, Gordana, Čolić, Miodrag, "Immunomodulatory Properties of Mesenchymal Stem Cells Derived from Dental Pulp and Dental Follicle are Susceptible to Activation by Toll-Like Receptor Agonists" in Stem Cells and Development, 20, no. 4 (2011):695-708,
https://doi.org/10.1089/scd.2010.0145 . .