TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Ilić, Nataša
AU  - Đokić, Jelena
AU  - Stojanović, Dušica
AU  - Vasilev, Saša
AU  - Gruden-Movsesijan, Alisa
AU  - Tomić, Sergej
PY  - 2023
UR  - https://www.microbiota-site.com/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2188
AB  - ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.
C3  - 10th ISM World Congress on Targeting Microbiota
T1  - NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION
EP  - 77
SP  - 77
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2188
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Ilić, Nataša and Đokić, Jelena and Stojanović, Dušica and Vasilev, Saša and Gruden-Movsesijan, Alisa and Tomić, Sergej",
year = "2023",
abstract = "ntroduction: Recent studies implicated overactivated myeloid cells and gut microbiome, along with our work, 
in multiple sclerosis (MS) pathogenesis. As we have shown before, prostaglandin (PG)E2 promotes 
suppressive properties of myeloid cells leading to amelioration of symptoms in myelin oligodendrocyte 
glycoprotein 
(MOG)-induced experimental autoimmune encephalomyelitis 
(EAE). Additionally, we 
investigated how the changes of gut microbiota associate with EAE and the effects of therapy.
Materials & Methods: MOG35-55 in Complete Freund Adjuvans was used for EAE induction in C57BL/6 
mice. Gold nanoparticles (GNP) conjugated with PGE2 and MOG were applied on the day 1, 3, 5, 7, and 9 
post-immunization. We performed extensive immunophenotyping and metagenomic analysis in order to 
decipher association between gut microbiome and efficacy of GNP-MOG-PGE2 treatment.
Results: GNP-MOG-PGE2 treatment alleviates EAE symptoms, decreased levels of pro-inflammatory 
cytokines in sera, and increased proportion of suppressive MDSCs in CNS-infiltrates. Furthermore, EAE 
induction significantly affected species richness, while GNP-MOG-PGE2 treatment increased the gut 
microbiota diversity and preserved the richness of species with immunomodulatory properties.
Conclusion: Taken together, our data indicate that targeted activation of myeloid cells by GNP-MOG-PGE2 
together with gut microbiota modification is very promising therapeutic strategy for MS.",
journal = "10th ISM World Congress on Targeting Microbiota",
title = "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION",
pages = "77-77",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2188"
}

Radojević, D., Bekić, M., Ilić, N., Đokić, J., Stojanović, D., Vasilev, S., Gruden-Movsesijan, A.,& Tomić, S.. (2023). NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota, 77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188

Radojević D, Bekić M, Ilić N, Đokić J, Stojanović D, Vasilev S, Gruden-Movsesijan A, Tomić S. NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION. in 10th ISM World Congress on Targeting Microbiota. 2023;:77-77.
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

Radojević, Dušan, Bekić, Marina, Ilić, Nataša, Đokić, Jelena, Stojanović, Dušica, Vasilev, Saša, Gruden-Movsesijan, Alisa, Tomić, Sergej, "NANOMATERIALS-BASED STRATEGY FOR MYELOID CELLS ACTIVATION RESULTS IN  EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AMELIORATION  AND GUT MICROBIOTA MODULATION" in 10th ISM World Congress on Targeting Microbiota (2023):77-77,
https://hdl.handle.net/21.15107/rcub_imagine_2188 .

TY  - CONF
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Gruden-Movsesijan, Alisa
AU  - Ilić, Nataša
AU  - Vasilev, Saša
AU  - Dinić, Miroslav
AU  - Golić, Nataša
AU  - Vučević, Dragana
AU  - Čolić, Miodrag
AU  - Tomić, Sergej
AU  - Đokić, Jelena
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1875
AB  - The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.
PB  - Novi Sad : Faculty of Sciences, Department of Biology and Ecology
C3  - Biologia Serbica
T1  - Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition
IS  - 1 (Special Edition)
SP  - 98
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1875
ER  - 

@conference{
author = "Radojević, Dušan and Bekić, Marina and Gruden-Movsesijan, Alisa and Ilić, Nataša and Vasilev, Saša and Dinić, Miroslav and Golić, Nataša and Vučević, Dragana and Čolić, Miodrag and Tomić, Sergej and Đokić, Jelena",
year = "2021",
abstract = "The role of gut microbiota composition in efficacy of various immune-based therapies is increasingly recognized.
Thus, the aim of our study was to investigate if the efficacy of myeloid-derived suppressor cells
(MDSC)-Prostaglandin E2 (PGE2) therapy for multiple sclerosis (MS) correlates with gut microbiota composition
and function. MDSC generated from bone marrow cells in the presence of PGE2 were applied to spinal
cord homogenate/CFA-induced experimental autoimmune encephalomyelitis (EAE) in Dark Agouti (DA)
rats, an animal model of MS. MDSC-PGE2 therapy resulted in a significant attenuation of EAE symptoms
over 30 days of disease monitoring. These results correlated with lower percentage of proinflammatory interferon-
gamma and interleukin-17 producing cells and higher percentage of anti-inflammatory IL-4 producing
cells in spinal cord and spleen. Gut microbial composition were studied using amplicon(16S rRNA)-based
metagenomic analyses of fecal samples collected prior to the induction of EAE and MDSC-PGE2 therapy application,
and at the peak of the disease. The induction of EAE resulted in a decrease of microbiota diversity,
whereas the MDSC-PGE2 therapy preserved the diversity in EAE-induced animals. The induction of EAE
in control group associated with a higher relative abundance of Peptococcaceae, but the lower levels of Veillonellaceae
and different groups of Prevotellaceae, known to produce immunosuppressive short chain fatty
acid (SCFA), and Lactobacillus reuteri, known for its anti-inflammatory function. In contrast, there were no
changes in levels of these immunoregulatory taxa in EAE-animals treated with MDSC-PGE2 therapy. Also,
SCFA producing Ruminococcaceae, and Coriobacteriaceae, known to metabolize phytoestrogens to immunosuppressive
metabolites were more abundant in EAE-animals treated with MDSC-PGE2 therapy. Predicted
metabolic profiling obtained by PICRUSt2 revealed that pathways involved in biosynthesis of polyamines,
metabolites known to contribute to homeostasis of gastrointestinal mucosa, were enriched in MDSC-PGE2
treated animals. Considering these results, the modification of gut microbiota composition and function
could further increase efficacy of MDSC-PGE-2 based therapy of autoimmune diseases.",
publisher = "Novi Sad : Faculty of Sciences, Department of Biology and Ecology",
journal = "Biologia Serbica",
title = "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition",
number = "1 (Special Edition)",
pages = "98",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1875"
}

Radojević, D., Bekić, M., Gruden-Movsesijan, A., Ilić, N., Vasilev, S., Dinić, M., Golić, N., Vučević, D., Čolić, M., Tomić, S.,& Đokić, J.. (2021). Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica
Novi Sad : Faculty of Sciences, Department of Biology and Ecology., 43(1 (Special Edition)), 98.
https://hdl.handle.net/21.15107/rcub_imagine_1875

Radojević D, Bekić M, Gruden-Movsesijan A, Ilić N, Vasilev S, Dinić M, Golić N, Vučević D, Čolić M, Tomić S, Đokić J. Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition. in Biologia Serbica. 2021;43(1 (Special Edition)):98.
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

Radojević, Dušan, Bekić, Marina, Gruden-Movsesijan, Alisa, Ilić, Nataša, Vasilev, Saša, Dinić, Miroslav, Golić, Nataša, Vučević, Dragana, Čolić, Miodrag, Tomić, Sergej, Đokić, Jelena, "Myeloid derived suppressor cells-therapy attenuates experimental autoimmune encephalomyelitis and modulates gut microbiota composition" in Biologia Serbica, 43, no. 1 (Special Edition) (2021):98,
https://hdl.handle.net/21.15107/rcub_imagine_1875 .

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 . .