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  - 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 . .