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  - Tertel, Tobias
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Radojević, Dušan
AU  - Stevanović, Dejan
AU  - Ilić, Nataša
AU  - Giebel, Bernd
AU  - Kosanović, Maja
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1517
AB  - COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13(+) and CD82(+) EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC(+) EVs than sera of the healthy donors and more CD24(+) EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.
PB  - Hoboken : Wiley
T2  - Journal of Extracellular Vesicles
T1  - Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients
IS  - 8
VL  - 11
DO  - 10.1002/jev2.12257
ER  - 

@article{
author = "Tertel, Tobias and Tomić, Sergej and Đokić, Jelena and Radojević, Dušan and Stevanović, Dejan and Ilić, Nataša and Giebel, Bernd and Kosanović, Maja",
year = "2022",
abstract = "COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13(+) and CD82(+) EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC(+) EVs than sera of the healthy donors and more CD24(+) EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.",
publisher = "Hoboken : Wiley",
journal = "Journal of Extracellular Vesicles",
title = "Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients",
number = "8",
volume = "11",
doi = "10.1002/jev2.12257"
}

Tertel, T., Tomić, S., Đokić, J., Radojević, D., Stevanović, D., Ilić, N., Giebel, B.,& Kosanović, M.. (2022). Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients. in Journal of Extracellular Vesicles
Hoboken : Wiley., 11(8).
https://doi.org/10.1002/jev2.12257

Tertel T, Tomić S, Đokić J, Radojević D, Stevanović D, Ilić N, Giebel B, Kosanović M. Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients. in Journal of Extracellular Vesicles. 2022;11(8).
doi:10.1002/jev2.12257 .

Tertel, Tobias, Tomić, Sergej, Đokić, Jelena, Radojević, Dušan, Stevanović, Dejan, Ilić, Nataša, Giebel, Bernd, Kosanović, Maja, "Serum-derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID-19 patients" in Journal of Extracellular Vesicles, 11, no. 8 (2022),
https://doi.org/10.1002/jev2.12257 . .

TY  - JOUR
AU  - Tomić, Sergej
AU  - Đokić, Jelena
AU  - Stevanović, Dejan
AU  - Ilić, Nataša
AU  - Gruden-Movsesijan, Alisa
AU  - Dinić, Miroslav
AU  - Radojević, Dušan
AU  - Bekić, Marina
AU  - Mitrović, Nebojša
AU  - Tomasević, Ratko
AU  - Mikić, Dragan
AU  - Stojanović, Dragos
AU  - Čolić, Miodrag
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1446
AB  - Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed similar to 140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with similar to 30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-gamma production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients
VL  - 12
DO  - 10.3389/fimmu.2021.614599
ER  - 

@article{
author = "Tomić, Sergej and Đokić, Jelena and Stevanović, Dejan and Ilić, Nataša and Gruden-Movsesijan, Alisa and Dinić, Miroslav and Radojević, Dušan and Bekić, Marina and Mitrović, Nebojša and Tomasević, Ratko and Mikić, Dragan and Stojanović, Dragos and Čolić, Miodrag",
year = "2021",
abstract = "Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed similar to 140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with similar to 30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-gamma production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients",
volume = "12",
doi = "10.3389/fimmu.2021.614599"
}

Tomić, S., Đokić, J., Stevanović, D., Ilić, N., Gruden-Movsesijan, A., Dinić, M., Radojević, D., Bekić, M., Mitrović, N., Tomasević, R., Mikić, D., Stojanović, D.,& Čolić, M.. (2021). Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 12.
https://doi.org/10.3389/fimmu.2021.614599

Tomić S, Đokić J, Stevanović D, Ilić N, Gruden-Movsesijan A, Dinić M, Radojević D, Bekić M, Mitrović N, Tomasević R, Mikić D, Stojanović D, Čolić M. Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients. in Frontiers in Immunology. 2021;12.
doi:10.3389/fimmu.2021.614599 .

Tomić, Sergej, Đokić, Jelena, Stevanović, Dejan, Ilić, Nataša, Gruden-Movsesijan, Alisa, Dinić, Miroslav, Radojević, Dušan, Bekić, Marina, Mitrović, Nebojša, Tomasević, Ratko, Mikić, Dragan, Stojanović, Dragos, Čolić, Miodrag, "Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients" in Frontiers in Immunology, 12 (2021),
https://doi.org/10.3389/fimmu.2021.614599 . .

TY  - CONF
AU  - Kosanović, Maja
AU  - Tertel, Tobias
AU  - Đokić, Jelena
AU  - Ilić, Nataša
AU  - Radojević, Dušan
AU  - Stevanović, Dejan
AU  - Movsesijan, Alisa Gruden
AU  - Giebel, Bernd
AU  - Tomić, Sergej
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1434
PB  - Wiley, Hoboken
C3  - European Journal of Immunology
T1  - Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity
EP  - 352
SP  - 352
VL  - 51
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1434
ER  - 

@conference{
author = "Kosanović, Maja and Tertel, Tobias and Đokić, Jelena and Ilić, Nataša and Radojević, Dušan and Stevanović, Dejan and Movsesijan, Alisa Gruden and Giebel, Bernd and Tomić, Sergej",
year = "2021",
publisher = "Wiley, Hoboken",
journal = "European Journal of Immunology",
title = "Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity",
pages = "352-352",
volume = "51",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1434"
}

Kosanović, M., Tertel, T., Đokić, J., Ilić, N., Radojević, D., Stevanović, D., Movsesijan, A. G., Giebel, B.,& Tomić, S.. (2021). Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity. in European Journal of Immunology
Wiley, Hoboken., 51, 352-352.
https://hdl.handle.net/21.15107/rcub_imagine_1434

Kosanović M, Tertel T, Đokić J, Ilić N, Radojević D, Stevanović D, Movsesijan AG, Giebel B, Tomić S. Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity. in European Journal of Immunology. 2021;51:352-352.
https://hdl.handle.net/21.15107/rcub_imagine_1434 .

Kosanović, Maja, Tertel, Tobias, Đokić, Jelena, Ilić, Nataša, Radojević, Dušan, Stevanović, Dejan, Movsesijan, Alisa Gruden, Giebel, Bernd, Tomić, Sergej, "Extracellular vesicles subtypes in sera of COVID-19 patients as indicators of immune dysregulation and disease severity" in European Journal of Immunology, 51 (2021):352-352,
https://hdl.handle.net/21.15107/rcub_imagine_1434 .

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 .