TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6643
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Lazarević, Milica
AU  - Kulaš, Jelena
AU  - Despotović, Sanja
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Koprivica, Ivan
AU  - Mirkov, Ivana
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6633
AB  - Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.
PB  - Elsevier B.V.
T2  - European Journal of Pharmacology
T1  - Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice
VL  - 971
DO  - 10.1016/j.ejphar.2024.176509
SP  - 176509
ER  - 

@article{
author = "Mićanović, Dragica and Lazarević, Milica and Kulaš, Jelena and Despotović, Sanja and Stegnjaić, Goran and Jevtić, Bojan and Koprivica, Ivan and Mirkov, Ivana and Stanisavljević, Suzana and Nikolovski, Neda and Miljković, Đorđe and Saksida, Tamara",
year = "2024",
abstract = "Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmacology",
title = "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice",
volume = "971",
doi = "10.1016/j.ejphar.2024.176509",
pages = "176509"
}

Mićanović, D., Lazarević, M., Kulaš, J., Despotović, S., Stegnjaić, G., Jevtić, B., Koprivica, I., Mirkov, I., Stanisavljević, S., Nikolovski, N., Miljković, Đ.,& Saksida, T.. (2024). Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology
Elsevier B.V.., 971, 176509.
https://doi.org/10.1016/j.ejphar.2024.176509

Mićanović D, Lazarević M, Kulaš J, Despotović S, Stegnjaić G, Jevtić B, Koprivica I, Mirkov I, Stanisavljević S, Nikolovski N, Miljković Đ, Saksida T. Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology. 2024;971:176509.
doi:10.1016/j.ejphar.2024.176509 .

Mićanović, Dragica, Lazarević, Milica, Kulaš, Jelena, Despotović, Sanja, Stegnjaić, Goran, Jevtić, Bojan, Koprivica, Ivan, Mirkov, Ivana, Stanisavljević, Suzana, Nikolovski, Neda, Miljković, Đorđe, Saksida, Tamara, "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice" in European Journal of Pharmacology, 971 (2024):176509,
https://doi.org/10.1016/j.ejphar.2024.176509 . .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Lazarević, Milica
AU  - Ignjatović, Đurđica
AU  - Tomić, Mirko
AU  - Nikolovski, Neda
AU  - Bjelobaba, Ivana
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6644
AB  - We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
PB  - Elsevier
T2  - Immunology Letters
T1  - Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate
VL  - 267
DO  - 10.1016/j.imlet.2024.106852
SP  - 106852
ER  - 

@article{
author = "Stegnjaić, Goran and Jevtić, Bojan and Lazarević, Milica and Ignjatović, Đurđica and Tomić, Mirko and Nikolovski, Neda and Bjelobaba, Ivana and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe and Stanisavljević, Suzana",
year = "2024",
abstract = "We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund’s adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.",
publisher = "Elsevier",
journal = "Immunology Letters",
title = "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate",
volume = "267",
doi = "10.1016/j.imlet.2024.106852",
pages = "106852"
}

Stegnjaić, G., Jevtić, B., Lazarević, M., Ignjatović, Đ., Tomić, M., Nikolovski, N., Bjelobaba, I., Momčilović, M., Dimitrijević, M., Miljković, Đ.,& Stanisavljević, S.. (2024). Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters
Elsevier., 267, 106852.
https://doi.org/10.1016/j.imlet.2024.106852

Stegnjaić G, Jevtić B, Lazarević M, Ignjatović Đ, Tomić M, Nikolovski N, Bjelobaba I, Momčilović M, Dimitrijević M, Miljković Đ, Stanisavljević S. Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate. in Immunology Letters. 2024;267:106852.
doi:10.1016/j.imlet.2024.106852 .

Stegnjaić, Goran, Jevtić, Bojan, Lazarević, Milica, Ignjatović, Đurđica, Tomić, Mirko, Nikolovski, Neda, Bjelobaba, Ivana, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, Stanisavljević, Suzana, "Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate" in Immunology Letters, 267 (2024):106852,
https://doi.org/10.1016/j.imlet.2024.106852 . .

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Lazarević, Milica
AU  - Kulaš, Jelena
AU  - Despotović, Sanja
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Koprivica, Ivan
AU  - Mirkov, Ivana
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6633
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6634
AB  - Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.
PB  - Elsevier B.V.
T2  - European Journal of Pharmacology
T1  - Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice
VL  - 971
DO  - 10.1016/j.ejphar.2024.176509
SP  - 176509
ER  - 

@article{
author = "Mićanović, Dragica and Lazarević, Milica and Kulaš, Jelena and Despotović, Sanja and Stegnjaić, Goran and Jevtić, Bojan and Koprivica, Ivan and Mirkov, Ivana and Stanisavljević, Suzana and Nikolovski, Neda and Miljković, Đorđe and Saksida, Tamara",
year = "2024",
abstract = "Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmacology",
title = "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice",
volume = "971",
doi = "10.1016/j.ejphar.2024.176509",
pages = "176509"
}

Mićanović, D., Lazarević, M., Kulaš, J., Despotović, S., Stegnjaić, G., Jevtić, B., Koprivica, I., Mirkov, I., Stanisavljević, S., Nikolovski, N., Miljković, Đ.,& Saksida, T.. (2024). Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology
Elsevier B.V.., 971, 176509.
https://doi.org/10.1016/j.ejphar.2024.176509

Mićanović D, Lazarević M, Kulaš J, Despotović S, Stegnjaić G, Jevtić B, Koprivica I, Mirkov I, Stanisavljević S, Nikolovski N, Miljković Đ, Saksida T. Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice. in European Journal of Pharmacology. 2024;971:176509.
doi:10.1016/j.ejphar.2024.176509 .

Mićanović, Dragica, Lazarević, Milica, Kulaš, Jelena, Despotović, Sanja, Stegnjaić, Goran, Jevtić, Bojan, Koprivica, Ivan, Mirkov, Ivana, Stanisavljević, Suzana, Nikolovski, Neda, Miljković, Đorđe, Saksida, Tamara, "Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice" in European Journal of Pharmacology, 971 (2024):176509,
https://doi.org/10.1016/j.ejphar.2024.176509 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Despotović, Sanja
AU  - Ignjatović, Đurđica
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Fraser, Graeme L
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6501
AB  - Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.
PB  - Springer Nature
T2  - Journal of Neuroinflammation
T1  - Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity
VL  - 21
DO  - 10.1186/s12974-024-03017-7
SP  - 26
ER  - 

@article{
author = "Lazarević, Milica and Stegnjaić, Goran and Jevtić, Bojan and Despotović, Sanja and Ignjatović, Đurđica and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Fraser, Graeme L and Dimitrijević, Mirjana and Miljković, Đorđe",
year = "2024",
abstract = "Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.",
publisher = "Springer Nature",
journal = "Journal of Neuroinflammation",
title = "Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity",
volume = "21",
doi = "10.1186/s12974-024-03017-7",
pages = "26"
}

Lazarević, M., Stegnjaić, G., Jevtić, B., Despotović, S., Ignjatović, Đ., Stanisavljević, S., Nikolovski, N., Momčilović, M., Fraser, G. L., Dimitrijević, M.,& Miljković, Đ.. (2024). Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity. in Journal of Neuroinflammation
Springer Nature., 21, 26.
https://doi.org/10.1186/s12974-024-03017-7

Lazarević M, Stegnjaić G, Jevtić B, Despotović S, Ignjatović Đ, Stanisavljević S, Nikolovski N, Momčilović M, Fraser GL, Dimitrijević M, Miljković Đ. Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity. in Journal of Neuroinflammation. 2024;21:26.
doi:10.1186/s12974-024-03017-7 .

Lazarević, Milica, Stegnjaić, Goran, Jevtić, Bojan, Despotović, Sanja, Ignjatović, Đurđica, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Fraser, Graeme L, Dimitrijević, Mirjana, Miljković, Đorđe, "Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity" in Journal of Neuroinflammation, 21 (2024):26,
https://doi.org/10.1186/s12974-024-03017-7 . .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Dimitrijević, Mirjana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6363
AB  - Experimental autoimmune encephalomyelitis (EAE) in inbred rodents commonly shows different clinical courses, so that the diseased animals can be clustered into four groups: mild. moderate, severe and lethal. Our aim was to determine biomolecular markers in the preclinical phase of EAE that allow the prediction of clinical course. 
Methods: Female Dark Agouti rats were immunized with spinal cord homogenate without adjuvant and examined for four weeks for clinical signs of EAE. Cells and sera from blood collected on days 0, 3, and 7 after immunization were processed for detection of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN) by "real-time" RT-PCR and ELISA, respectively. 
Results: Induction of EAE resulted in the downregulation of IFN and TNF in the preclinical phase of disease, whereas IL-1 and IL-6 expression levels were unaffected. However, there was no correlation between the relative expression of IFN or TNF and the cumulative clinical score (sum of daily clinical scores), suggesting that they are not predictive markers of EAE severity. Our preliminary results that suggest a negative correlation between IL-1 expression level before EAE induction and cumulative score require further justification. 
Conclusion: The proinflammatory cytokines investigated so far in our study cannot be considered as good biomarkers of EAE severity. However, the downregulation of IFN and TNF in the blood cells during the asymptomatic phase of EAE suggests that they enter the central nervous system early from the bloodstream, which argues for the study of chemokine and/or chemokine receptors expression as potential biomarkers for the clinical courses of EAE.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate
SP  - 89
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6363
ER  - 

@conference{
author = "Stegnjaić, Goran and Lazarević, Milica and Jevtić, Bojan and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Mostarica Stojković, Marija and Miljković, Đorđe and Dimitrijević, Mirjana",
year = "2023",
abstract = "Experimental autoimmune encephalomyelitis (EAE) in inbred rodents commonly shows different clinical courses, so that the diseased animals can be clustered into four groups: mild. moderate, severe and lethal. Our aim was to determine biomolecular markers in the preclinical phase of EAE that allow the prediction of clinical course. 
Methods: Female Dark Agouti rats were immunized with spinal cord homogenate without adjuvant and examined for four weeks for clinical signs of EAE. Cells and sera from blood collected on days 0, 3, and 7 after immunization were processed for detection of proinflammatory cytokines (IL-1, IL-6, TNF, and IFN) by "real-time" RT-PCR and ELISA, respectively. 
Results: Induction of EAE resulted in the downregulation of IFN and TNF in the preclinical phase of disease, whereas IL-1 and IL-6 expression levels were unaffected. However, there was no correlation between the relative expression of IFN or TNF and the cumulative clinical score (sum of daily clinical scores), suggesting that they are not predictive markers of EAE severity. Our preliminary results that suggest a negative correlation between IL-1 expression level before EAE induction and cumulative score require further justification. 
Conclusion: The proinflammatory cytokines investigated so far in our study cannot be considered as good biomarkers of EAE severity. However, the downregulation of IFN and TNF in the blood cells during the asymptomatic phase of EAE suggests that they enter the central nervous system early from the bloodstream, which argues for the study of chemokine and/or chemokine receptors expression as potential biomarkers for the clinical courses of EAE.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate",
pages = "89",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6363"
}

Stegnjaić, G., Lazarević, M., Jevtić, B., Stanisavljević, S., Nikolovski, N., Momčilović, M., Mostarica Stojković, M., Miljković, Đ.,& Dimitrijević, M.. (2023). Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 89.
https://hdl.handle.net/21.15107/rcub_ibiss_6363

Stegnjaić G, Lazarević M, Jevtić B, Stanisavljević S, Nikolovski N, Momčilović M, Mostarica Stojković M, Miljković Đ, Dimitrijević M. Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:89.
https://hdl.handle.net/21.15107/rcub_ibiss_6363 .

Stegnjaić, Goran, Lazarević, Milica, Jevtić, Bojan, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Mostarica Stojković, Marija, Miljković, Đorđe, Dimitrijević, Mirjana, "Molecular biomarkers as a prognostic tool for clinical courses of experimental autoimmune encephalomyelitis in rats immunized with spinal cord homogenate" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):89,
https://hdl.handle.net/21.15107/rcub_ibiss_6363 .

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Stanisavljević, Suzana
AU  - Mićanović, Dragica
AU  - Jevtić, Bojan
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6294
AB  - Innate lymphoid cells type 3 (ILC3s) are the first line sentinels at the mucous
tissues, where they contribute to the homeostatic immune response in a major
way. Also, they have been increasingly appreciated as important modulators of
chronic inflammatory and autoimmune responses, both locally and systemically.
The proper identification of ILC3 is of utmost importance for meaningful studies
on their role in immunity. Flow cytometry is the method of choice for the
detection and characterization of ILC3. However, the analysis of ILC3-related
papers shows inconsistency in ILC3 phenotypic definition, as different inclusion
and exclusion markers are used for their identification. Here, we present these
discrepancies in the phenotypic characterization of human and mouse ILC3s. We
discuss the pros and cons of using various markers for ILC3 identification.
Furthermore, we consider the possibilities for the efficient isolation and
propagation of ILC3 from different organs and tissues for in-vitro and in-vivo
studies. This paper calls upon uniformity in ILC3 definition, isolation, and
propagation for the increased possibility of confluent interpretation of ILC3’s
role in immunity.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Immunology
T1  - ILC3: a case of conflicted identity
VL  - 14
DO  - 10.3389/fimmu.2023.1271699
SP  - 1271699
ER  - 

@article{
author = "Koprivica, Ivan and Stanisavljević, Suzana and Mićanović, Dragica and Jevtić, Bojan and Stojanović, Ivana D. and Miljković, Đorđe",
year = "2023",
abstract = "Innate lymphoid cells type 3 (ILC3s) are the first line sentinels at the mucous
tissues, where they contribute to the homeostatic immune response in a major
way. Also, they have been increasingly appreciated as important modulators of
chronic inflammatory and autoimmune responses, both locally and systemically.
The proper identification of ILC3 is of utmost importance for meaningful studies
on their role in immunity. Flow cytometry is the method of choice for the
detection and characterization of ILC3. However, the analysis of ILC3-related
papers shows inconsistency in ILC3 phenotypic definition, as different inclusion
and exclusion markers are used for their identification. Here, we present these
discrepancies in the phenotypic characterization of human and mouse ILC3s. We
discuss the pros and cons of using various markers for ILC3 identification.
Furthermore, we consider the possibilities for the efficient isolation and
propagation of ILC3 from different organs and tissues for in-vitro and in-vivo
studies. This paper calls upon uniformity in ILC3 definition, isolation, and
propagation for the increased possibility of confluent interpretation of ILC3’s
role in immunity.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Immunology",
title = "ILC3: a case of conflicted identity",
volume = "14",
doi = "10.3389/fimmu.2023.1271699",
pages = "1271699"
}

Koprivica, I., Stanisavljević, S., Mićanović, D., Jevtić, B., Stojanović, I. D.,& Miljković, Đ.. (2023). ILC3: a case of conflicted identity. in Frontiers in Immunology
Lausanne: Frontiers Media SA., 14, 1271699.
https://doi.org/10.3389/fimmu.2023.1271699

Koprivica I, Stanisavljević S, Mićanović D, Jevtić B, Stojanović ID, Miljković Đ. ILC3: a case of conflicted identity. in Frontiers in Immunology. 2023;14:1271699.
doi:10.3389/fimmu.2023.1271699 .

Koprivica, Ivan, Stanisavljević, Suzana, Mićanović, Dragica, Jevtić, Bojan, Stojanović, Ivana D., Miljković, Đorđe, "ILC3: a case of conflicted identity" in Frontiers in Immunology, 14 (2023):1271699,
https://doi.org/10.3389/fimmu.2023.1271699 . .

TY  - CONF
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Dimitrijević, Mirjana
AU  - Miljković, Đorđe
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6300
AB  - Experimental autoimmune encephalomyelitis (EAE) is commonly induced with
central nervous system antigens mixed with complete Freund’s adjuvant (CFA). This
adjuvant has a confounding influence on the translational capacity of EAE as multiple
sclerosis (MS) model. Thus, we developed a novel subtype of EAE induced in Dark
Agouti (DA) rats with spinal cord homogenate (SCH) without CFA and characterized
it as a reliable MS model. Despite genetic homogeneity of experimental animals and
controlled environmental conditions, we observed variations in EAE clinical course in
SCH-immunized DA rats and four clinical groups were identified: lethal, severe,
moderate, and mild. Immune cells of spinal cord, small intestine lamina propria and
lymph nodes draining the site of immunization were compared between moderate and
severe group. Higher numbers of CD4+ T cells, regulatory T cells (Treg), helper T
cells type 1 (Th1) and 17 (Th17), and B cells were detected in the spinal cords of
severe group. Also, higher levels of interferon (IFN)-γ and interleukin (IL)-6 and an
increased proportion of Th1 and Th17 cells were detected in the lamina propria of the
severe group. Aminoguanidine – an inducible nitric oxide synthase inhibitor that was
applied to the rats during the effector phase of the disease ameliorated EAE and
imposed a shift of clinical outcomes towards milder variants. Our results suggest that
different clinical outcomes in DA rats come as a consequence of variability in the
strength of the effector mechanisms exerted within the CNS. The study of the
underlying mechanisms for the observed variability is necessary.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6300
ER  - 

@conference{
author = "Lazarević, Milica and Stegnjaić, Goran and Jevtić, Bojan and Stanisavljević, Suzana and Nikolovski, Neda and Momčilović, Miljana and Dimitrijević, Mirjana and Miljković, Đorđe",
year = "2023",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is commonly induced with
central nervous system antigens mixed with complete Freund’s adjuvant (CFA). This
adjuvant has a confounding influence on the translational capacity of EAE as multiple
sclerosis (MS) model. Thus, we developed a novel subtype of EAE induced in Dark
Agouti (DA) rats with spinal cord homogenate (SCH) without CFA and characterized
it as a reliable MS model. Despite genetic homogeneity of experimental animals and
controlled environmental conditions, we observed variations in EAE clinical course in
SCH-immunized DA rats and four clinical groups were identified: lethal, severe,
moderate, and mild. Immune cells of spinal cord, small intestine lamina propria and
lymph nodes draining the site of immunization were compared between moderate and
severe group. Higher numbers of CD4+ T cells, regulatory T cells (Treg), helper T
cells type 1 (Th1) and 17 (Th17), and B cells were detected in the spinal cords of
severe group. Also, higher levels of interferon (IFN)-γ and interleukin (IL)-6 and an
increased proportion of Th1 and Th17 cells were detected in the lamina propria of the
severe group. Aminoguanidine – an inducible nitric oxide synthase inhibitor that was
applied to the rats during the effector phase of the disease ameliorated EAE and
imposed a shift of clinical outcomes towards milder variants. Our results suggest that
different clinical outcomes in DA rats come as a consequence of variability in the
strength of the effector mechanisms exerted within the CNS. The study of the
underlying mechanisms for the observed variability is necessary.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats",
pages = "42",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6300"
}

Lazarević, M., Stegnjaić, G., Jevtić, B., Stanisavljević, S., Nikolovski, N., Momčilović, M., Dimitrijević, M.,& Miljković, Đ.. (2023). Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 42.
https://hdl.handle.net/21.15107/rcub_ibiss_6300

Lazarević M, Stegnjaić G, Jevtić B, Stanisavljević S, Nikolovski N, Momčilović M, Dimitrijević M, Miljković Đ. Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:42.
https://hdl.handle.net/21.15107/rcub_ibiss_6300 .

Lazarević, Milica, Stegnjaić, Goran, Jevtić, Bojan, Stanisavljević, Suzana, Nikolovski, Neda, Momčilović, Miljana, Dimitrijević, Mirjana, Miljković, Đorđe, "Distinct clinical outcomes of Complete Freund’s adjuvant-free experimental autoimmune encephalomyelitis induced in DA rats" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):42,
https://hdl.handle.net/21.15107/rcub_ibiss_6300 .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Tsiailanis, Antonios D.
AU  - Lazarević, Milica
AU  - Gkalpinos, Vasileios K.
AU  - Nikolovski, Neda
AU  - Antoniou, Thomas
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas G.
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5305
AB  - Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.
PB  - Basel: MDPI
T2  - Molecules
T1  - Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis
IS  - 24
VL  - 27
DO  - 10.3390/molecules27248770
SP  - 8770
ER  - 

@article{
author = "Stegnjaić, Goran and Tsiailanis, Antonios D. and Lazarević, Milica and Gkalpinos, Vasileios K. and Nikolovski, Neda and Antoniou, Thomas and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G. and Jevtić, Bojan",
year = "2022",
abstract = "Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis",
number = "24",
volume = "27",
doi = "10.3390/molecules27248770",
pages = "8770"
}

Stegnjaić, G., Tsiailanis, A. D., Lazarević, M., Gkalpinos, V. K., Nikolovski, N., Antoniou, T., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules
Basel: MDPI., 27(24), 8770.
https://doi.org/10.3390/molecules27248770

Stegnjaić G, Tsiailanis AD, Lazarević M, Gkalpinos VK, Nikolovski N, Antoniou T, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules. 2022;27(24):8770.
doi:10.3390/molecules27248770 .

Stegnjaić, Goran, Tsiailanis, Antonios D., Lazarević, Milica, Gkalpinos, Vasileios K., Nikolovski, Neda, Antoniou, Thomas, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G., Jevtić, Bojan, "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis" in Molecules, 27, no. 24 (2022):8770,
https://doi.org/10.3390/molecules27248770 . .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Tsiailanis, Antonios D
AU  - Antoniou, Thomas
AU  - Gkalpinos, Vasileios K
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas G
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6299
AB  - This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - The effect of a gallic acid derivative on encephalitogenic cells
SP  - 140
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6299
ER  - 

@conference{
author = "Stegnjaić, Goran and Lazarević, Milica and Tsiailanis, Antonios D and Antoniou, Thomas and Gkalpinos, Vasileios K and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G and Jevtić, Bojan",
year = "2022",
abstract = "This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "The effect of a gallic acid derivative on encephalitogenic cells",
pages = "140",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6299"
}

Stegnjaić, G., Lazarević, M., Tsiailanis, A. D., Antoniou, T., Gkalpinos, V. K., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). The effect of a gallic acid derivative on encephalitogenic cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299

Stegnjaić G, Lazarević M, Tsiailanis AD, Antoniou T, Gkalpinos VK, Nikolovski N, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. The effect of a gallic acid derivative on encephalitogenic cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

Stegnjaić, Goran, Lazarević, Milica, Tsiailanis, Antonios D, Antoniou, Thomas, Gkalpinos, Vasileios K, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G, Jevtić, Bojan, "The effect of a gallic acid derivative on encephalitogenic cells" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):140,
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

TY  - CONF
AU  - Mićanović, Dragica
AU  - Nikolovski, Neda
AU  - Koprivica, Ivan
AU  - Despotović, Sanja
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Momčilović, Miljana
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5770
AB  - Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима.
AB  - Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
T1  - Etil-piruvat i autoimunske bolesti
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5770
ER  - 

@conference{
author = "Mićanović, Dragica and Nikolovski, Neda and Koprivica, Ivan and Despotović, Sanja and Jevtić, Bojan and Stanisavljević, Suzana and Momčilović, Miljana and Pejnović, Nada and Stojanović, Ivana D. and Miljković, Đorđe and Saksida, Tamara",
year = "2022",
abstract = "Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима., Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia",
title = "Etil-piruvat i autoimunske bolesti",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5770"
}

Mićanović, D., Nikolovski, N., Koprivica, I., Despotović, S., Jevtić, B., Stanisavljević, S., Momčilović, M., Pejnović, N., Stojanović, I. D., Miljković, Đ.,& Saksida, T.. (2022). Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5770

Mićanović D, Nikolovski N, Koprivica I, Despotović S, Jevtić B, Stanisavljević S, Momčilović M, Pejnović N, Stojanović ID, Miljković Đ, Saksida T. Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .

Mićanović, Dragica, Nikolovski, Neda, Koprivica, Ivan, Despotović, Sanja, Jevtić, Bojan, Stanisavljević, Suzana, Momčilović, Miljana, Pejnović, Nada, Stojanović, Ivana D., Miljković, Đorđe, Saksida, Tamara, "Etil-piruvat i autoimunske bolesti" in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Diamantis, Dimitrois A
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Tzakos, Andreas G
AU  - Miljković, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5085
AB  - Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.
PB  - Amsterdam : Elsevier
T2  - Immunology Letters
T1  - Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis
VL  - 251-252
DO  - 10.1016/j.imlet.2022.09.006
SP  - 9
EP  - 19
ER  - 

@article{
author = "Stegnjaić, Goran and Lazarević, Milica and Diamantis, Dimitrois A and Nikolovski, Neda and Jevtić, Bojan and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Tzakos, Andreas G and Miljković, Đorđe",
year = "2022",
abstract = "Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.",
publisher = "Amsterdam : Elsevier",
journal = "Immunology Letters",
title = "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis",
volume = "251-252",
doi = "10.1016/j.imlet.2022.09.006",
pages = "9-19"
}

Stegnjaić, G., Lazarević, M., Diamantis, D. A., Nikolovski, N., Jevtić, B., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Tzakos, A. G.,& Miljković, Đ.. (2022). Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters
Amsterdam : Elsevier., 251-252, 9-19.
https://doi.org/10.1016/j.imlet.2022.09.006

Stegnjaić G, Lazarević M, Diamantis DA, Nikolovski N, Jevtić B, Stanisavljević S, Dimitrijević M, Momčilović M, Tzakos AG, Miljković Đ. Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters. 2022;251-252:9-19.
doi:10.1016/j.imlet.2022.09.006 .

Stegnjaić, Goran, Lazarević, Milica, Diamantis, Dimitrois A, Nikolovski, Neda, Jevtić, Bojan, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Tzakos, Andreas G, Miljković, Đorđe, "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis" in Immunology Letters, 251-252 (2022):9-19,
https://doi.org/10.1016/j.imlet.2022.09.006 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Stegnjaić, Goran
AU  - Krishnamoorthy, Gurumoorthy
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Jevtić, Bojan
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4200
AB  - Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.
PB  - Elsevier BV
T2  - Journal of Neuroimmunology
T1  - Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.
VL  - 354
DO  - 10.1016/j.jneuroim.2021.577547
SP  - 577547
ER  - 

@article{
author = "Lazarević, Milica and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Stegnjaić, Goran and Krishnamoorthy, Gurumoorthy and Mostarica Stojković, Marija and Miljković, Đorđe and Jevtić, Bojan",
year = "2021",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.",
publisher = "Elsevier BV",
journal = "Journal of Neuroimmunology",
title = "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.",
volume = "354",
doi = "10.1016/j.jneuroim.2021.577547",
pages = "577547"
}

Lazarević, M., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Stegnjaić, G., Krishnamoorthy, G., Mostarica Stojković, M., Miljković, Đ.,& Jevtić, B.. (2021). Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology
Elsevier BV., 354, 577547.
https://doi.org/10.1016/j.jneuroim.2021.577547

Lazarević M, Nikolovski N, Stanisavljević S, Dimitrijević M, Stegnjaić G, Krishnamoorthy G, Mostarica Stojković M, Miljković Đ, Jevtić B. Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology. 2021;354:577547.
doi:10.1016/j.jneuroim.2021.577547 .

Lazarević, Milica, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Stegnjaić, Goran, Krishnamoorthy, Gurumoorthy, Mostarica Stojković, Marija, Miljković, Đorđe, Jevtić, Bojan, "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies." in Journal of Neuroimmunology, 354 (2021):577547,
https://doi.org/10.1016/j.jneuroim.2021.577547 . .

TY  - JOUR
AU  - Lazarević, Milica
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Stegnjaić, Goran
AU  - Krishnamoorthy, Gurumoorthy
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Jevtić, Bojan
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4193
AB  - Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.
PB  - Elsevier BV
T2  - Journal of Neuroimmunology
T1  - Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.
VL  - 354
DO  - 10.1016/j.jneuroim.2021.577547
SP  - 577547
ER  - 

@article{
author = "Lazarević, Milica and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Stegnjaić, Goran and Krishnamoorthy, Gurumoorthy and Mostarica Stojković, Marija and Miljković, Đorđe and Jevtić, Bojan",
year = "2021",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.",
publisher = "Elsevier BV",
journal = "Journal of Neuroimmunology",
title = "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.",
volume = "354",
doi = "10.1016/j.jneuroim.2021.577547",
pages = "577547"
}

Lazarević, M., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Stegnjaić, G., Krishnamoorthy, G., Mostarica Stojković, M., Miljković, Đ.,& Jevtić, B.. (2021). Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology
Elsevier BV., 354, 577547.
https://doi.org/10.1016/j.jneuroim.2021.577547

Lazarević M, Nikolovski N, Stanisavljević S, Dimitrijević M, Stegnjaić G, Krishnamoorthy G, Mostarica Stojković M, Miljković Đ, Jevtić B. Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies.. in Journal of Neuroimmunology. 2021;354:577547.
doi:10.1016/j.jneuroim.2021.577547 .

Lazarević, Milica, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Stegnjaić, Goran, Krishnamoorthy, Gurumoorthy, Mostarica Stojković, Marija, Miljković, Đorđe, Jevtić, Bojan, "Complete Freund's adjuvant-free experimental autoimmune encephalomyelitis in Dark Agouti rats is a valuable tool for multiple sclerosis studies." in Journal of Neuroimmunology, 354 (2021):577547,
https://doi.org/10.1016/j.jneuroim.2021.577547 . .

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Stanisavljević, Suzana
AU  - Jensen, Isaac J
AU  - Griffith, Thomas S
AU  - Badovinac, Vladimir P
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0165247821001176
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4455
AB  - Sepsis is a life-threatening condition characterized by an acute cytokine storm followed by prolonged dysfunction of the immune system in the survivors. Post-septic lymphopenia and functional deficits of the remaining immune cells lead to increased susceptibility to secondary infections and other morbid conditions causing late death in the patients. This state of post-septic immunoparalysis may also influence disorders stemming from inappropriate or overactive immune responses, such as autoimmune and immunoinflammatory diseases, including multiple sclerosis. In addition, ongoing autoimmunity likely influences the susceptibility to and outcome of sepsis. This review article addresses the bidirectional relationship between sepsis and multiple sclerosis, with a focus on the immunologic mechanisms of the interaction and potential directions for future studies.
PB  - Amsterdam: Elsevier B.V.
T2  - Immunology Letters
T1  - Sepsis and multiple sclerosis: Causative links and outcomes
VL  - 238
DO  - 10.1016/j.imlet.2021.07.008
SP  - 40
EP  - 46
ER  - 

@article{
author = "Miljković, Đorđe and Stanisavljević, Suzana and Jensen, Isaac J and Griffith, Thomas S and Badovinac, Vladimir P",
year = "2021",
abstract = "Sepsis is a life-threatening condition characterized by an acute cytokine storm followed by prolonged dysfunction of the immune system in the survivors. Post-septic lymphopenia and functional deficits of the remaining immune cells lead to increased susceptibility to secondary infections and other morbid conditions causing late death in the patients. This state of post-septic immunoparalysis may also influence disorders stemming from inappropriate or overactive immune responses, such as autoimmune and immunoinflammatory diseases, including multiple sclerosis. In addition, ongoing autoimmunity likely influences the susceptibility to and outcome of sepsis. This review article addresses the bidirectional relationship between sepsis and multiple sclerosis, with a focus on the immunologic mechanisms of the interaction and potential directions for future studies.",
publisher = "Amsterdam: Elsevier B.V.",
journal = "Immunology Letters",
title = "Sepsis and multiple sclerosis: Causative links and outcomes",
volume = "238",
doi = "10.1016/j.imlet.2021.07.008",
pages = "40-46"
}

Miljković, Đ., Stanisavljević, S., Jensen, I. J., Griffith, T. S.,& Badovinac, V. P.. (2021). Sepsis and multiple sclerosis: Causative links and outcomes. in Immunology Letters
Amsterdam: Elsevier B.V.., 238, 40-46.
https://doi.org/10.1016/j.imlet.2021.07.008

Miljković Đ, Stanisavljević S, Jensen IJ, Griffith TS, Badovinac VP. Sepsis and multiple sclerosis: Causative links and outcomes. in Immunology Letters. 2021;238:40-46.
doi:10.1016/j.imlet.2021.07.008 .

Miljković, Đorđe, Stanisavljević, Suzana, Jensen, Isaac J, Griffith, Thomas S, Badovinac, Vladimir P, "Sepsis and multiple sclerosis: Causative links and outcomes" in Immunology Letters, 238 (2021):40-46,
https://doi.org/10.1016/j.imlet.2021.07.008 . .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Čepić, Aleksa
AU  - Bojić, Svetlana
AU  - Veljović, Katarina
AU  - Mihajlović, Sanja
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Momčilović, Miljana
AU  - Lazarević, Milica
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
AU  - Golić, Nataša
PY  - 2019
UR  - http://www.nature.com/articles/s41598-018-37505-7
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6351648
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3264
AB  - Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.
T2  - Scientific Reports
T1  - Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.
IS  - 1
VL  - 9
DO  - 10.1038/s41598-018-37505-7
SP  - 918
ER  - 

@article{
author = "Stanisavljević, Suzana and Čepić, Aleksa and Bojić, Svetlana and Veljović, Katarina and Mihajlović, Sanja and Nikolovski, Neda and Jevtić, Bojan and Momčilović, Miljana and Lazarević, Milica and Mostarica Stojković, Marija and Miljković, Đorđe and Golić, Nataša",
year = "2019",
abstract = "Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.",
journal = "Scientific Reports",
title = "Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.",
number = "1",
volume = "9",
doi = "10.1038/s41598-018-37505-7",
pages = "918"
}

Stanisavljević, S., Čepić, A., Bojić, S., Veljović, K., Mihajlović, S., Nikolovski, N., Jevtić, B., Momčilović, M., Lazarević, M., Mostarica Stojković, M., Miljković, Đ.,& Golić, N.. (2019). Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.. in Scientific Reports, 9(1), 918.
https://doi.org/10.1038/s41598-018-37505-7

Stanisavljević S, Čepić A, Bojić S, Veljović K, Mihajlović S, Nikolovski N, Jevtić B, Momčilović M, Lazarević M, Mostarica Stojković M, Miljković Đ, Golić N. Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats.. in Scientific Reports. 2019;9(1):918.
doi:10.1038/s41598-018-37505-7 .

Stanisavljević, Suzana, Čepić, Aleksa, Bojić, Svetlana, Veljović, Katarina, Mihajlović, Sanja, Nikolovski, Neda, Jevtić, Bojan, Momčilović, Miljana, Lazarević, Milica, Mostarica Stojković, Marija, Miljković, Đorđe, Golić, Nataša, "Oral neonatal antibiotic treatment perturbs gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats." in Scientific Reports, 9, no. 1 (2019):918,
https://doi.org/10.1038/s41598-018-37505-7 . .

TY  - BOOK
PY  - 2019
UR  - https://plus.sr.cobiss.net/opac7/bib/281009420
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3558
UR  - https://www.isos.rs/congress-2019
AB  - Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book. Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia; 2019. 136 p.
PB  - Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade
PB  - Belgrade: Immunological Society of Serbia
T2  - Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade : Immunological Society of Serbia
T1  - Immunology at the Confluence of Multidisciplinary Approaches : abstract book
SP  - 1
EP  - 136
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3558
ER  - 

@book{
editor = "Saksida, Tamara, Stanisavljević, Suzana, Miljković, Đorđe",
year = "2019",
abstract = "Saksida T, Stanisavljević S, Miljković Đ, editors. Immunology at the Confluence of Multidisciplinary Approaches : abstract book. Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade; Immunological Society of Serbia; 2019. 136 p.",
publisher = "Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade: Immunological Society of Serbia",
journal = "Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade : Immunological Society of Serbia",
title = "Immunology at the Confluence of Multidisciplinary Approaches : abstract book",
pages = "1-136",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3558"
}

Saksida, T., Stanisavljević, S.,& Miljković, Đ.. (2019). Immunology at the Confluence of Multidisciplinary Approaches : abstract book. in Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade : Immunological Society of Serbia
Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade., 1-136.
https://hdl.handle.net/21.15107/rcub_ibiss_3558

Saksida T, Stanisavljević S, Miljković Đ. Immunology at the Confluence of Multidisciplinary Approaches : abstract book. in Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade : Immunological Society of Serbia. 2019;:1-136.
https://hdl.handle.net/21.15107/rcub_ibiss_3558 .

Saksida, Tamara, Stanisavljević, Suzana, Miljković, Đorđe, "Immunology at the Confluence of Multidisciplinary Approaches : abstract book" in Belgrade : Institute for Biological Research "Siniša Stanković", University of Belgrade : Immunological Society of Serbia (2019):1-136,
https://hdl.handle.net/21.15107/rcub_ibiss_3558 .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Dinić, Miroslav
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Momčilović, Miljana
AU  - Đokić, Jelena
AU  - Golić, Nataša
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
PY  - 2018
UR  - http://journal.frontiersin.org/article/10.3389/fimmu.2018.00942/full
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5942155
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3056
AB  - Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.
T2  - Frontiers in Immunology
T1  - Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.
VL  - 9
DO  - 10.3389/fimmu.2018.00942
SP  - 942
ER  - 

@article{
author = "Stanisavljević, Suzana and Dinić, Miroslav and Jevtić, Bojan and Nikolovski, Neda and Momčilović, Miljana and Đokić, Jelena and Golić, Nataša and Mostarica Stojković, Marija and Miljković, Đorđe",
year = "2018",
abstract = "Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.",
journal = "Frontiers in Immunology",
title = "Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.",
volume = "9",
doi = "10.3389/fimmu.2018.00942",
pages = "942"
}

Stanisavljević, S., Dinić, M., Jevtić, B., Nikolovski, N., Momčilović, M., Đokić, J., Golić, N., Mostarica Stojković, M.,& Miljković, Đ.. (2018). Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.. in Frontiers in Immunology, 9, 942.
https://doi.org/10.3389/fimmu.2018.00942

Stanisavljević S, Dinić M, Jevtić B, Nikolovski N, Momčilović M, Đokić J, Golić N, Mostarica Stojković M, Miljković Đ. Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.. in Frontiers in Immunology. 2018;9:942.
doi:10.3389/fimmu.2018.00942 .

Stanisavljević, Suzana, Dinić, Miroslav, Jevtić, Bojan, Nikolovski, Neda, Momčilović, Miljana, Đokić, Jelena, Golić, Nataša, Mostarica Stojković, Marija, Miljković, Đorđe, "Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis." in Frontiers in Immunology, 9 (2018):942,
https://doi.org/10.3389/fimmu.2018.00942 . .

TY  - THES
AU  - Stanisavljević, Suzana
PY  - 2018
UR  - http://uvidok.rcub.bg.ac.rs/handle/123456789/2612
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3105
AB  - Multipla skleroza je hronična, inflamacijska, neurodegenerativna, demijelinizirajuća bolest centralnog nervnog sistema (CNS). Etiologija multiple skleroze još uvek nije poznata, ali je sve više podataka koji pokazuju ulogu crevne mikrobiote u patogenezi bolesti. Više podataka o značaju crevne mikrobiote u autoimunosti CNS dobijeno je istraživanjima na eksperimentalnom autoimunskom encefalomijelitisu (EAE), životinjskom modelu multiple skleroze. U EAE-u se autoimunski odgovor protiv CNS-a pokreće u limfnim čvorovima koji dreniraju mesto imunizacije, gde se CD4+ T ćelije specifične za antigene CNS-a aktiviraju i diferenciraju u Th (engl. T helper) 1 ćelije koje produkuju IFN-γ i Th17 ćelije koje produkuju IL-17. Kada dospeju u CNS ove Th ćelije bivaju reaktivirane od strane lokalnih antigen-prezentujućih ćelija. Nakon reaktivacije, encefalitogene Th ćelije pokreću i održavaju inflamaciju unutar CNS-a. Albino oksford (AO) pacovi su veoma otporni na indukciju EAE-a. S druge strane, Dark Agouti (DA) pacovi razvijaju EAE čak i nakon blage imunizacije. U dosadašnjim istraživanjima je pokazano da se AO pacovi u odnosu na DA pacove razlikuju po slaboj aktivaciji Th1 i Th17 ćelija u relevantnim limfnim čvorovima u odgovoru na encefalitogenu imunizaciju. Takođe, pokazano je da relativno mali broj encefalitogenih ćelija infiltrira CNS AO pacova. Do sada nije vršeno ispitivanje uloge GALT-a i mikrobiote creva u otpornosti pacova soja AO na indukciju EAE-a. Sve je više istraživanja koja pokazuju da mikroorganizmi creva imaju važnu ulogu u regulaciji imunskog odgovora kroz interakciju sa limfnim tkivom creva (GALT, engl. gut-associated lymphoid tissue). U istraživanjima na EAE-u je pokazano da određeni mikroorganizmi creva pospešuju tok bolesti, dok drugi ostvaruju terapeutske efekte modulacijom odnosa Th1 i Th17 encefalitogenih ćelija i regulatornih T ćelija (Treg). Poznato je i da encefalitogene CD4+ T ćelije migriraju u GALT, uključujući mezenterične limfne čvorove i Pejerove ploče gde se mogu diferencirati u Treg. Smatra se da značajnu ulogu u ovoj rediferencijaciji imaju crevne bakterije i njihovi produkti. Zbog toga je važno utvrditi koje bakterije u crevima i na koji način ostvaruju ulogu u patogenezi multiple skleroze, kako bi se modulacijom mikrobiote creva omogućila prevencija i tretman bolesti. Nedavna uporedna istraživanja sastava mikrobiote creva osoba obolelih od multiple skleroze i zdravih osoba pokazuju kod pacijenata povećanu ili smanjenu zastupljenost pojedinih grupa bakterija, uključujući Clostridia klaster XIV i IV, Bacteroides fragilis, i rodova Pseudomonas, Mycoplana, Haemophilus, Dorea i Blautia. Međutim, rezultati dosadašnjih istraživanja nisu dovoljni da bi bilo razjašnjeno na koji način mikrobiota creva doprinosi patogenezi multiple skleroze. Mikrobiota creva i GALT se smatraju važnim učesnicima u pokretanju, propagaciji, ali i u prevenciji autoimunoskih procesa u CNS-u. Sastav mikrobiote creva se razlikuje kod pacijenata obolelih od multiple skleroze i zdravih osoba. U skladu sa tim, soj pacova podložan EAE-u, DA, i soj koji je otporan na indukciju EAE-a, AO, pokazali su razlike u sastavu mikrobiote creva u ovom istraživanju. Konkretno, Turicibacter sp. i članovi Lachnospiraceae familije su identifikovani kao mogući promoteri otpornosti na indukciju EAE-a ili oporavka od EAE-a. Takođe je pokazano da se ćelijski sastav mezenteričnih limfnih čvorova, kao i ćelijski sastav Pejerovih ploča razlikuje između AO i DA pacova, s tim da DA pacovi imaju više CD4+ ćelija, ali i više Treg-a. Pored toga, ćelije GALT-a AO soja pacova otpornog na EAE su produkovale manje IFN-γ i IL-17 u poređenju sa DA sojem pacova koji je podložan indukciji EAE-a. Produkcija IL-10 kao glavnog imunoregulatornog citokina u crevima koji ispoljava imunosupresivne efekte, razlikovala se između ova dva soja pacova. Antibiotski tretman je narušio otpornost AO pacova prema indukciji EAE-a, što se ogledalo u pojavi blagih kliničkih simptoma, povećanom broju infiltrata u kičmenoj moždini i povišenom nivou IL-17 u CNS-u. Primena antibiotika je dovela i do promena u drenirajućim limfnim čvorovima. U njima je primećen povećan broj ćelija sa povećanom zastupljenošću CD4+ T ćelija, koje su, produkovale više proinflamacijskih citokina. Analiza zastupljenosti Treg je pokazala da se procenat Treg razlikuje između sojeva samo u Pejerovim pločama neimunizovanih životinja, dok se nakon imunizacije smanjuje udeo Treg u drenirajućim limfnim čvorovima, mezenteričnim limfnim čvorovima i Pejerovim pločama kod životinja tretiranih antibioticima. Sastav mikrobiote creva AO pacova se znatno promenio nakon četiri nedelje primene antibiotika, nakon čega su se promene izgubile. Transferom mikrobiote creva AO pacova u DA pacove došlo je do ublažavanja simptoma EAE-a kod DA pacova. U CNS-u dolazi do smanjenja koncentracije IL-17 kod tako tretiranih DA životinja. Uočena je povećana celularnost u drenirajućim limfnim čvorovima, kao i veća zastupljenost Treg u drenirajućim i mezenteričnim limfnim čvorovima. Transfer mikrobiote je doveo i do značajne promene diverziteta crevne mikrobiote tretiranih DA pacova. Promene se naročito zapažaju u diverzitetu mlečnokiselinskih bakterija. Rezultati ove doktrorske disertacije jasno pokazuju da crevna mikrobiota ima bitnu ulogu u patogenezi autoimunskog procesa prisutnog u CNS-u i da bi njena modulacija mogla biti novi pristup u terapiji multiple skleroze.
AB  - Multiple sclerosis is a chronic inflammatory neurodegenerative demyelinating disease of the central nervous system (CNS). Etiology of multiple sclerosis is still unknown, but data are showing that gut microbiota plays an important role in the pathogenesis of this disease. Information about the significance of gut microbiota in CNS autoimmunity has been dominantly obtained in studies in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The autoimmune response against CNS starts in lymph nodes draining the site of immunization in EAE. There, CD4+ T cells are being activated and differentiated into Th1 (helper T cells) and Th17 cells that produce IFN-γ and IL-17, respectively. When Th cells arrive in the CNS, they are reactivated by local antigen-presenting cells. After the reactivation, these encephalitogenic T cells initiate and propagate CNS inflammation.
Albino Oxford (AO) rats are highly resistant to EAE induction. On the other hand, Dark Agouti (DA) rats develop EAE even after the mild immunization. In our earlier studies it was shown that AO rats had less activated Th1 and Th17 cells in the relevant lymph nodes in response to encephalitogenic immunization, unlike DA rats. Also, it was shown that relatively small number of encephalitogenic cells infiltrated CNS in AO rats. Up until now, the studies of role of GALT and gut microbiota in resistance of AO rats in EAE induction have not been conducted.
It has been increasingly appreciated that gut microbiota plays an important role in the regulation of the immune response through interaction with the cells of gut-associated lymphoid tissue (GALT). In EAE studies specific gut microorganisms have been proposed to promote the disease, while others have been shown to have therapeutic effects by modulating ratio and activity of encefalitogenic Th1 and Th17 cells and regulatory T cells (Treg). Encefalitogenic cells can also migrate to GALT, including mesenteric lymph nodes and Peyer’s patches, where they can be re-differentiated into
Treg. It is considered that intrinsic bacteria and their products play an important role in this re-differentiation. That is why it has become important to determine which bacteria and in what ways are implicated in multiple sclerosis pathogenesis, to prevent and treat the disease by modulating gut microbiota. Recent comparative studies of gut microbiota content of multiple sclerosis patients and healthy individuals have shown increased presence of some groups of bacteria in patients, including Clostridia clusters XIV and IV, Bacteroides fragilis, and Pseudomonas, Mycoplana, Haemophilus, Dorea, Blautia. However, the results of previous studies cannot clarify what are the mechanisms of contribution of gut microbiota to pathogenesis of multiple sclerosis.
Gut microbiota and GALT are considered to be important players in initiation, propagation, but also in prevention of CNS autoimmunity. Gut microbiota content differs among multiple sclerosis patients and healthy subjects. In accordance to that, EAE-resistant rat strain and EAE-prone rat strain have different gut microbiota content in our experiments. Specifically, Turicibacter sp. and members of Lachnospiraceae family are identified as possible promoters of EAE resistance or EAE recovery. Besides, it was demonstrated that mesenteric lymph nodes and Peyer’s patches differ between AO and DA rats. DA rats have higher proportion of CD4+ cells and more Tregs. Further, GALT cells of EAE-resistant rat strain produced less IFN-γ and IL-17 in comparison to EAE-prone rat strain. Production of IL-10, major immunoregulatory cytokine, was also different among these rat strains.
Antibiotic treatment disturbed EAE resistance in AO rats. It was observed in the form of mild clinical symptoms, higher number of spinal cord infiltrates and a higher concentration of IL-17 in the CNS. Antibiotic effects were seen in lymph nodes draining the site of immunization; they had higher cellularity, a higher proportion of CD4+ cells, and higher production of proinflammatory cytokines. Treg analysis showed that there was a difference in Peyer’s patches of unimmunized rats. After the immunization, less Treg was observed in draining lymph nodes, mesenteric lymph nodes and Peyer’s patches in antibiotic treated rats. Gut microbiota content of AO rats was significantly changed after four weeks of antibiotic treatment.
Gut microbiota transfer from AO rats into DA rats resulted in milder EAE symptoms in DA rats and lower concentration of IL-17 in CNS. Increased proportion of
Treg was observed in draining lymph nodes in the treated animals. Gut microbiota transfer led to more significant changes in gut microbiota diversity of treated rats, especially in lactic acid bacteria.
Results of this doctoral thesis clearly demonstrate important role of gut microbiota in the pathogenesis of the CNS autoimmunity. They also imply that modulation of gut microbiota could be used as a novel therapeutic approach in multiple sclerosis.
PB  - Belgrade: Universiy of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Uloga mikrobiote i limfnog tkiva creva u otpornosti pacova soja Albino Oksford na indukciju eksperimentalnog autoimunskog encefalomijelitisa
T1  - Role of gut microbiota and gut-associated lymphoid tissue in resistance of Albino Oxford rats to experimental autoimmune encephalomyelitis induction
SP  - 1
EP  - 134
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_3105
ER  - 

@phdthesis{
author = "Stanisavljević, Suzana",
year = "2018",
abstract = "Multipla skleroza je hronična, inflamacijska, neurodegenerativna, demijelinizirajuća bolest centralnog nervnog sistema (CNS). Etiologija multiple skleroze još uvek nije poznata, ali je sve više podataka koji pokazuju ulogu crevne mikrobiote u patogenezi bolesti. Više podataka o značaju crevne mikrobiote u autoimunosti CNS dobijeno je istraživanjima na eksperimentalnom autoimunskom encefalomijelitisu (EAE), životinjskom modelu multiple skleroze. U EAE-u se autoimunski odgovor protiv CNS-a pokreće u limfnim čvorovima koji dreniraju mesto imunizacije, gde se CD4+ T ćelije specifične za antigene CNS-a aktiviraju i diferenciraju u Th (engl. T helper) 1 ćelije koje produkuju IFN-γ i Th17 ćelije koje produkuju IL-17. Kada dospeju u CNS ove Th ćelije bivaju reaktivirane od strane lokalnih antigen-prezentujućih ćelija. Nakon reaktivacije, encefalitogene Th ćelije pokreću i održavaju inflamaciju unutar CNS-a. Albino oksford (AO) pacovi su veoma otporni na indukciju EAE-a. S druge strane, Dark Agouti (DA) pacovi razvijaju EAE čak i nakon blage imunizacije. U dosadašnjim istraživanjima je pokazano da se AO pacovi u odnosu na DA pacove razlikuju po slaboj aktivaciji Th1 i Th17 ćelija u relevantnim limfnim čvorovima u odgovoru na encefalitogenu imunizaciju. Takođe, pokazano je da relativno mali broj encefalitogenih ćelija infiltrira CNS AO pacova. Do sada nije vršeno ispitivanje uloge GALT-a i mikrobiote creva u otpornosti pacova soja AO na indukciju EAE-a. Sve je više istraživanja koja pokazuju da mikroorganizmi creva imaju važnu ulogu u regulaciji imunskog odgovora kroz interakciju sa limfnim tkivom creva (GALT, engl. gut-associated lymphoid tissue). U istraživanjima na EAE-u je pokazano da određeni mikroorganizmi creva pospešuju tok bolesti, dok drugi ostvaruju terapeutske efekte modulacijom odnosa Th1 i Th17 encefalitogenih ćelija i regulatornih T ćelija (Treg). Poznato je i da encefalitogene CD4+ T ćelije migriraju u GALT, uključujući mezenterične limfne čvorove i Pejerove ploče gde se mogu diferencirati u Treg. Smatra se da značajnu ulogu u ovoj rediferencijaciji imaju crevne bakterije i njihovi produkti. Zbog toga je važno utvrditi koje bakterije u crevima i na koji način ostvaruju ulogu u patogenezi multiple skleroze, kako bi se modulacijom mikrobiote creva omogućila prevencija i tretman bolesti. Nedavna uporedna istraživanja sastava mikrobiote creva osoba obolelih od multiple skleroze i zdravih osoba pokazuju kod pacijenata povećanu ili smanjenu zastupljenost pojedinih grupa bakterija, uključujući Clostridia klaster XIV i IV, Bacteroides fragilis, i rodova Pseudomonas, Mycoplana, Haemophilus, Dorea i Blautia. Međutim, rezultati dosadašnjih istraživanja nisu dovoljni da bi bilo razjašnjeno na koji način mikrobiota creva doprinosi patogenezi multiple skleroze. Mikrobiota creva i GALT se smatraju važnim učesnicima u pokretanju, propagaciji, ali i u prevenciji autoimunoskih procesa u CNS-u. Sastav mikrobiote creva se razlikuje kod pacijenata obolelih od multiple skleroze i zdravih osoba. U skladu sa tim, soj pacova podložan EAE-u, DA, i soj koji je otporan na indukciju EAE-a, AO, pokazali su razlike u sastavu mikrobiote creva u ovom istraživanju. Konkretno, Turicibacter sp. i članovi Lachnospiraceae familije su identifikovani kao mogući promoteri otpornosti na indukciju EAE-a ili oporavka od EAE-a. Takođe je pokazano da se ćelijski sastav mezenteričnih limfnih čvorova, kao i ćelijski sastav Pejerovih ploča razlikuje između AO i DA pacova, s tim da DA pacovi imaju više CD4+ ćelija, ali i više Treg-a. Pored toga, ćelije GALT-a AO soja pacova otpornog na EAE su produkovale manje IFN-γ i IL-17 u poređenju sa DA sojem pacova koji je podložan indukciji EAE-a. Produkcija IL-10 kao glavnog imunoregulatornog citokina u crevima koji ispoljava imunosupresivne efekte, razlikovala se između ova dva soja pacova. Antibiotski tretman je narušio otpornost AO pacova prema indukciji EAE-a, što se ogledalo u pojavi blagih kliničkih simptoma, povećanom broju infiltrata u kičmenoj moždini i povišenom nivou IL-17 u CNS-u. Primena antibiotika je dovela i do promena u drenirajućim limfnim čvorovima. U njima je primećen povećan broj ćelija sa povećanom zastupljenošću CD4+ T ćelija, koje su, produkovale više proinflamacijskih citokina. Analiza zastupljenosti Treg je pokazala da se procenat Treg razlikuje između sojeva samo u Pejerovim pločama neimunizovanih životinja, dok se nakon imunizacije smanjuje udeo Treg u drenirajućim limfnim čvorovima, mezenteričnim limfnim čvorovima i Pejerovim pločama kod životinja tretiranih antibioticima. Sastav mikrobiote creva AO pacova se znatno promenio nakon četiri nedelje primene antibiotika, nakon čega su se promene izgubile. Transferom mikrobiote creva AO pacova u DA pacove došlo je do ublažavanja simptoma EAE-a kod DA pacova. U CNS-u dolazi do smanjenja koncentracije IL-17 kod tako tretiranih DA životinja. Uočena je povećana celularnost u drenirajućim limfnim čvorovima, kao i veća zastupljenost Treg u drenirajućim i mezenteričnim limfnim čvorovima. Transfer mikrobiote je doveo i do značajne promene diverziteta crevne mikrobiote tretiranih DA pacova. Promene se naročito zapažaju u diverzitetu mlečnokiselinskih bakterija. Rezultati ove doktrorske disertacije jasno pokazuju da crevna mikrobiota ima bitnu ulogu u patogenezi autoimunskog procesa prisutnog u CNS-u i da bi njena modulacija mogla biti novi pristup u terapiji multiple skleroze., Multiple sclerosis is a chronic inflammatory neurodegenerative demyelinating disease of the central nervous system (CNS). Etiology of multiple sclerosis is still unknown, but data are showing that gut microbiota plays an important role in the pathogenesis of this disease. Information about the significance of gut microbiota in CNS autoimmunity has been dominantly obtained in studies in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The autoimmune response against CNS starts in lymph nodes draining the site of immunization in EAE. There, CD4+ T cells are being activated and differentiated into Th1 (helper T cells) and Th17 cells that produce IFN-γ and IL-17, respectively. When Th cells arrive in the CNS, they are reactivated by local antigen-presenting cells. After the reactivation, these encephalitogenic T cells initiate and propagate CNS inflammation.
Albino Oxford (AO) rats are highly resistant to EAE induction. On the other hand, Dark Agouti (DA) rats develop EAE even after the mild immunization. In our earlier studies it was shown that AO rats had less activated Th1 and Th17 cells in the relevant lymph nodes in response to encephalitogenic immunization, unlike DA rats. Also, it was shown that relatively small number of encephalitogenic cells infiltrated CNS in AO rats. Up until now, the studies of role of GALT and gut microbiota in resistance of AO rats in EAE induction have not been conducted.
It has been increasingly appreciated that gut microbiota plays an important role in the regulation of the immune response through interaction with the cells of gut-associated lymphoid tissue (GALT). In EAE studies specific gut microorganisms have been proposed to promote the disease, while others have been shown to have therapeutic effects by modulating ratio and activity of encefalitogenic Th1 and Th17 cells and regulatory T cells (Treg). Encefalitogenic cells can also migrate to GALT, including mesenteric lymph nodes and Peyer’s patches, where they can be re-differentiated into
Treg. It is considered that intrinsic bacteria and their products play an important role in this re-differentiation. That is why it has become important to determine which bacteria and in what ways are implicated in multiple sclerosis pathogenesis, to prevent and treat the disease by modulating gut microbiota. Recent comparative studies of gut microbiota content of multiple sclerosis patients and healthy individuals have shown increased presence of some groups of bacteria in patients, including Clostridia clusters XIV and IV, Bacteroides fragilis, and Pseudomonas, Mycoplana, Haemophilus, Dorea, Blautia. However, the results of previous studies cannot clarify what are the mechanisms of contribution of gut microbiota to pathogenesis of multiple sclerosis.
Gut microbiota and GALT are considered to be important players in initiation, propagation, but also in prevention of CNS autoimmunity. Gut microbiota content differs among multiple sclerosis patients and healthy subjects. In accordance to that, EAE-resistant rat strain and EAE-prone rat strain have different gut microbiota content in our experiments. Specifically, Turicibacter sp. and members of Lachnospiraceae family are identified as possible promoters of EAE resistance or EAE recovery. Besides, it was demonstrated that mesenteric lymph nodes and Peyer’s patches differ between AO and DA rats. DA rats have higher proportion of CD4+ cells and more Tregs. Further, GALT cells of EAE-resistant rat strain produced less IFN-γ and IL-17 in comparison to EAE-prone rat strain. Production of IL-10, major immunoregulatory cytokine, was also different among these rat strains.
Antibiotic treatment disturbed EAE resistance in AO rats. It was observed in the form of mild clinical symptoms, higher number of spinal cord infiltrates and a higher concentration of IL-17 in the CNS. Antibiotic effects were seen in lymph nodes draining the site of immunization; they had higher cellularity, a higher proportion of CD4+ cells, and higher production of proinflammatory cytokines. Treg analysis showed that there was a difference in Peyer’s patches of unimmunized rats. After the immunization, less Treg was observed in draining lymph nodes, mesenteric lymph nodes and Peyer’s patches in antibiotic treated rats. Gut microbiota content of AO rats was significantly changed after four weeks of antibiotic treatment.
Gut microbiota transfer from AO rats into DA rats resulted in milder EAE symptoms in DA rats and lower concentration of IL-17 in CNS. Increased proportion of
Treg was observed in draining lymph nodes in the treated animals. Gut microbiota transfer led to more significant changes in gut microbiota diversity of treated rats, especially in lactic acid bacteria.
Results of this doctoral thesis clearly demonstrate important role of gut microbiota in the pathogenesis of the CNS autoimmunity. They also imply that modulation of gut microbiota could be used as a novel therapeutic approach in multiple sclerosis.",
publisher = "Belgrade: Universiy of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Uloga mikrobiote i limfnog tkiva creva u otpornosti pacova soja Albino Oksford na indukciju eksperimentalnog autoimunskog encefalomijelitisa, Role of gut microbiota and gut-associated lymphoid tissue in resistance of Albino Oxford rats to experimental autoimmune encephalomyelitis induction",
pages = "1-134",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_3105"
}

Stanisavljević, S.. (2018). Uloga mikrobiote i limfnog tkiva creva u otpornosti pacova soja Albino Oksford na indukciju eksperimentalnog autoimunskog encefalomijelitisa. in University of Belgrade, Faculty of Biology
Belgrade: Universiy of Belgrade, Faculty of Biology., 1-134.
https://hdl.handle.net/21.15107/rcub_ibiss_3105

Stanisavljević S. Uloga mikrobiote i limfnog tkiva creva u otpornosti pacova soja Albino Oksford na indukciju eksperimentalnog autoimunskog encefalomijelitisa. in University of Belgrade, Faculty of Biology. 2018;:1-134.
https://hdl.handle.net/21.15107/rcub_ibiss_3105 .

Stanisavljević, Suzana, "Uloga mikrobiote i limfnog tkiva creva u otpornosti pacova soja Albino Oksford na indukciju eksperimentalnog autoimunskog encefalomijelitisa" in University of Belgrade, Faculty of Biology (2018):1-134,
https://hdl.handle.net/21.15107/rcub_ibiss_3105 .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Šavikin, Katarina
AU  - Nikolovski, Neda
AU  - Živković, Jelena
AU  - Saksida, Tamara
AU  - Momčilović, Miljana
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Stanisavljević, Suzana
AU  - Miljković, Đorđe
AU  - Menković, Nebojša
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1756464617303353
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2793
AB  - Pomegranate peel extract (PPE) was obtained by aqueous-ethanol extraction and was abundant in punicalin, punicalagin and ellagic acid. As these compounds are known to act against inflammation and oxidative stress in synergistic fashion, effects of PPE were tested in vitro on immune cells and in animal models of multiple sclerosis and type 1 diabetes (T1D). In vitro, PPE inhibited interleukin-17 (IL-17) production from gut-associated lymphoid tissue (GALT) cells. PPE also reduced production of IL-17 in activated T cells isolated from animals with experimental autoimmune encephalomyelitis (EAE). It efficiently down-regulated clinical symptoms of EAE in DA rats and of streptozotocin-induced T1D in C57BL/6 mice. The effect of PPE in T1D was mediated by inhibition of immune cell infiltration into pancreatic islets and through interference with IL-17 and IFN-γ production in GALT. Our results suggest that PPE has the potential to be used as phytopharmaceutical for certain autoimmune and chronic inflammatory disorders.
T2  - Journal of Functional Foods
T1  - Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes
VL  - 35
DO  - 10.1016/j.jff.2017.06.021
SP  - 522
EP  - 530
ER  - 

@article{
author = "Stojanović, Ivana D. and Šavikin, Katarina and Nikolovski, Neda and Živković, Jelena and Saksida, Tamara and Momčilović, Miljana and Koprivica, Ivan and Vujičić, Milica and Stanisavljević, Suzana and Miljković, Đorđe and Menković, Nebojša",
year = "2017",
abstract = "Pomegranate peel extract (PPE) was obtained by aqueous-ethanol extraction and was abundant in punicalin, punicalagin and ellagic acid. As these compounds are known to act against inflammation and oxidative stress in synergistic fashion, effects of PPE were tested in vitro on immune cells and in animal models of multiple sclerosis and type 1 diabetes (T1D). In vitro, PPE inhibited interleukin-17 (IL-17) production from gut-associated lymphoid tissue (GALT) cells. PPE also reduced production of IL-17 in activated T cells isolated from animals with experimental autoimmune encephalomyelitis (EAE). It efficiently down-regulated clinical symptoms of EAE in DA rats and of streptozotocin-induced T1D in C57BL/6 mice. The effect of PPE in T1D was mediated by inhibition of immune cell infiltration into pancreatic islets and through interference with IL-17 and IFN-γ production in GALT. Our results suggest that PPE has the potential to be used as phytopharmaceutical for certain autoimmune and chronic inflammatory disorders.",
journal = "Journal of Functional Foods",
title = "Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes",
volume = "35",
doi = "10.1016/j.jff.2017.06.021",
pages = "522-530"
}

Stojanović, I. D., Šavikin, K., Nikolovski, N., Živković, J., Saksida, T., Momčilović, M., Koprivica, I., Vujičić, M., Stanisavljević, S., Miljković, Đ.,& Menković, N.. (2017). Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes. in Journal of Functional Foods, 35, 522-530.
https://doi.org/10.1016/j.jff.2017.06.021

Stojanović ID, Šavikin K, Nikolovski N, Živković J, Saksida T, Momčilović M, Koprivica I, Vujičić M, Stanisavljević S, Miljković Đ, Menković N. Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes. in Journal of Functional Foods. 2017;35:522-530.
doi:10.1016/j.jff.2017.06.021 .

Stojanović, Ivana D., Šavikin, Katarina, Nikolovski, Neda, Živković, Jelena, Saksida, Tamara, Momčilović, Miljana, Koprivica, Ivan, Vujičić, Milica, Stanisavljević, Suzana, Miljković, Đorđe, Menković, Nebojša, "Pomegranate peel extract ameliorates autoimmunity in animal models of multiple sclerosis and type 1 diabetes" in Journal of Functional Foods, 35 (2017):522-530,
https://doi.org/10.1016/j.jff.2017.06.021 . .

TY  - JOUR
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Gašić, Uroš
AU  - Mišić, Danijela
AU  - Despotović, Jovana
AU  - Samardžić, Jelena
AU  - Miljković, Đorđe
AU  - Timotijević, Gordana
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1756464617304486
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2832
AB  - Cucumber (Cucumis sativus) fruit has been used in cuisine worldwide, while its leaves are rich in immunomodulatory compounds. Cucumber leaf extract (CLE) was characterized by the predominance of triterpenoids cucurbitacins and significant levels of phenolics. Effects of CLE on CD4 + T helper (Th) cells and macrophages, as the major encephalitogenic cells in the autoimmunity of the central nervous system were investigated in our study. CLE potently inhibited production of major pathogenic Th cytokines: interferon-gamma and interleukin-17, as well as of nitric oxide and reactive oxygen species in macrophages. Antigen-presenting activity of macrophages and dendritic cells was also affected by CLE. The effects of CLE were co-incident with modulation of NFκB and p38 MAPK signaling. Concentrations of CLE used in vitro did not show toxic effects on zebrafish embryos. Moreover, CLE inhibited generation of encephalitogenic cells in vivo. These results demonstrate that CLE deserve further investigation on its anti-encephalitogenic therapeutic properties.
T2  - Journal of Functional Foods
T1  - Anti-encephalitogenic effects of cucumber leaf extract
VL  - 37
DO  - 10.1016/j.jff.2017.07.060
SP  - 249
EP  - 262
ER  - 

@article{
author = "Jevtić, Bojan and Nikolovski, Neda and Stanisavljević, Suzana and Gašić, Uroš and Mišić, Danijela and Despotović, Jovana and Samardžić, Jelena and Miljković, Đorđe and Timotijević, Gordana",
year = "2017",
abstract = "Cucumber (Cucumis sativus) fruit has been used in cuisine worldwide, while its leaves are rich in immunomodulatory compounds. Cucumber leaf extract (CLE) was characterized by the predominance of triterpenoids cucurbitacins and significant levels of phenolics. Effects of CLE on CD4 + T helper (Th) cells and macrophages, as the major encephalitogenic cells in the autoimmunity of the central nervous system were investigated in our study. CLE potently inhibited production of major pathogenic Th cytokines: interferon-gamma and interleukin-17, as well as of nitric oxide and reactive oxygen species in macrophages. Antigen-presenting activity of macrophages and dendritic cells was also affected by CLE. The effects of CLE were co-incident with modulation of NFκB and p38 MAPK signaling. Concentrations of CLE used in vitro did not show toxic effects on zebrafish embryos. Moreover, CLE inhibited generation of encephalitogenic cells in vivo. These results demonstrate that CLE deserve further investigation on its anti-encephalitogenic therapeutic properties.",
journal = "Journal of Functional Foods",
title = "Anti-encephalitogenic effects of cucumber leaf extract",
volume = "37",
doi = "10.1016/j.jff.2017.07.060",
pages = "249-262"
}

Jevtić, B., Nikolovski, N., Stanisavljević, S., Gašić, U., Mišić, D., Despotović, J., Samardžić, J., Miljković, Đ.,& Timotijević, G.. (2017). Anti-encephalitogenic effects of cucumber leaf extract. in Journal of Functional Foods, 37, 249-262.
https://doi.org/10.1016/j.jff.2017.07.060

Jevtić B, Nikolovski N, Stanisavljević S, Gašić U, Mišić D, Despotović J, Samardžić J, Miljković Đ, Timotijević G. Anti-encephalitogenic effects of cucumber leaf extract. in Journal of Functional Foods. 2017;37:249-262.
doi:10.1016/j.jff.2017.07.060 .

Jevtić, Bojan, Nikolovski, Neda, Stanisavljević, Suzana, Gašić, Uroš, Mišić, Danijela, Despotović, Jovana, Samardžić, Jelena, Miljković, Đorđe, Timotijević, Gordana, "Anti-encephalitogenic effects of cucumber leaf extract" in Journal of Functional Foods, 37 (2017):249-262,
https://doi.org/10.1016/j.jff.2017.07.060 . .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Nikolovski, Neda
AU  - Vujičić, Milica
AU  - Saksida, Tamara
AU  - Jevtić, Bojan
AU  - Milovanović, Boško
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0165247817301979
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2854
AB  - C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4 + T cell populations in mesenteric lymph nodes and Peyer's p atches of these mouse strains. Lower proportion of Treg was observed in NOD PP, Th2 cells dominated in BALB/c mice in mesenteric lymph nodes (MLN) and Peyer's patches (PP), while Th1 cells prevailed in C57BL/6 MLN. Intradermal immunization of mice with complete Freund's adjuvant resulted in significant difference in Th cell distribution in GALT of NOD mice. Differences were less pronounced in C57BL/6 mice, while GALT of BALB/c mice was almost unresponsive to the immunization. The observed strain- and tissue-dependent changes in Treg proportion after the immunization was probably a consequence of different CCR2 or CCR6-related migration patterns and/or in situ Treg proliferation. In conclusion, NOD, a highly autoimmunity-prone mouse strain, exhibits more profound GALT-related immune response upon immunization compared to the strains that are less prone to autoimmunity.
T2  - Immunology Letters
T1  - Strain-specific helper T cell profile in the gut-associated lymphoid tissue
VL  - 190
DO  - 10.1016/j.imlet.2017.08.017
SP  - 282
EP  - 288
ER  - 

@article{
author = "Stanisavljević, Suzana and Nikolovski, Neda and Vujičić, Milica and Saksida, Tamara and Jevtić, Bojan and Milovanović, Boško and Momčilović, Miljana and Miljković, Đorđe and Stojanović, Ivana D.",
year = "2017",
abstract = "C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4 + T cell populations in mesenteric lymph nodes and Peyer's p atches of these mouse strains. Lower proportion of Treg was observed in NOD PP, Th2 cells dominated in BALB/c mice in mesenteric lymph nodes (MLN) and Peyer's patches (PP), while Th1 cells prevailed in C57BL/6 MLN. Intradermal immunization of mice with complete Freund's adjuvant resulted in significant difference in Th cell distribution in GALT of NOD mice. Differences were less pronounced in C57BL/6 mice, while GALT of BALB/c mice was almost unresponsive to the immunization. The observed strain- and tissue-dependent changes in Treg proportion after the immunization was probably a consequence of different CCR2 or CCR6-related migration patterns and/or in situ Treg proliferation. In conclusion, NOD, a highly autoimmunity-prone mouse strain, exhibits more profound GALT-related immune response upon immunization compared to the strains that are less prone to autoimmunity.",
journal = "Immunology Letters",
title = "Strain-specific helper T cell profile in the gut-associated lymphoid tissue",
volume = "190",
doi = "10.1016/j.imlet.2017.08.017",
pages = "282-288"
}

Stanisavljević, S., Nikolovski, N., Vujičić, M., Saksida, T., Jevtić, B., Milovanović, B., Momčilović, M., Miljković, Đ.,& Stojanović, I. D.. (2017). Strain-specific helper T cell profile in the gut-associated lymphoid tissue. in Immunology Letters, 190, 282-288.
https://doi.org/10.1016/j.imlet.2017.08.017

Stanisavljević S, Nikolovski N, Vujičić M, Saksida T, Jevtić B, Milovanović B, Momčilović M, Miljković Đ, Stojanović ID. Strain-specific helper T cell profile in the gut-associated lymphoid tissue. in Immunology Letters. 2017;190:282-288.
doi:10.1016/j.imlet.2017.08.017 .

Stanisavljević, Suzana, Nikolovski, Neda, Vujičić, Milica, Saksida, Tamara, Jevtić, Bojan, Milovanović, Boško, Momčilović, Miljana, Miljković, Đorđe, Stojanović, Ivana D., "Strain-specific helper T cell profile in the gut-associated lymphoid tissue" in Immunology Letters, 190 (2017):282-288,
https://doi.org/10.1016/j.imlet.2017.08.017 . .

TY  - JOUR
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Jevtić, Bojan
AU  - Momčilović, Miljana
AU  - Lavrnja, Irena
AU  - Miljković, Đorđe
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0753332217331694
UR  - http://www.sciencedirect.com/science/article/pii/S0753332217331694
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2864
AB  - Ethyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS). Here, in vivo effects of ethyl pyruvate on EAE are thoroughly investigated in the CNS and within the gut associated lymphoid tissue. Ethyl pyruvate reduced infiltrates within the CNS and number of activated macrophages/microglia (ED1(+)/Iba1(+)) and proliferating astrocytes (GFAP(+)). Furthermore, it reduced expression of HMGB1 in activated macrophages/microglia. It also reduced number of activated T cells and antigen-presenting cells and expression of Th1/Th17-related molecules in mesenteric lymph nodes and Peyer's patches. These results contribute to our understanding of anti-encephalitogenic effects of ethyl pyruvate as they provide evidence of its effects within the CNS and imply that these effects are related to reduction of inflammatory immune response in gut associated lymphoid tissue.
T2  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
T1  - Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.
VL  - 96
DO  - 10.1016/j.biopha.2017.09.110
SP  - 78
EP  - 85
ER  - 

@article{
author = "Nikolovski, Neda and Stanisavljević, Suzana and Jevtić, Bojan and Momčilović, Miljana and Lavrnja, Irena and Miljković, Đorđe",
year = "2017",
abstract = "Ethyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS). Here, in vivo effects of ethyl pyruvate on EAE are thoroughly investigated in the CNS and within the gut associated lymphoid tissue. Ethyl pyruvate reduced infiltrates within the CNS and number of activated macrophages/microglia (ED1(+)/Iba1(+)) and proliferating astrocytes (GFAP(+)). Furthermore, it reduced expression of HMGB1 in activated macrophages/microglia. It also reduced number of activated T cells and antigen-presenting cells and expression of Th1/Th17-related molecules in mesenteric lymph nodes and Peyer's patches. These results contribute to our understanding of anti-encephalitogenic effects of ethyl pyruvate as they provide evidence of its effects within the CNS and imply that these effects are related to reduction of inflammatory immune response in gut associated lymphoid tissue.",
journal = "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie",
title = "Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.",
volume = "96",
doi = "10.1016/j.biopha.2017.09.110",
pages = "78-85"
}

Nikolovski, N., Stanisavljević, S., Jevtić, B., Momčilović, M., Lavrnja, I.,& Miljković, Đ.. (2017). Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.. in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 96, 78-85.
https://doi.org/10.1016/j.biopha.2017.09.110

Nikolovski N, Stanisavljević S, Jevtić B, Momčilović M, Lavrnja I, Miljković Đ. Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut.. in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2017;96:78-85.
doi:10.1016/j.biopha.2017.09.110 .

Nikolovski, Neda, Stanisavljević, Suzana, Jevtić, Bojan, Momčilović, Miljana, Lavrnja, Irena, Miljković, Đorđe, "Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut." in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 96 (2017):78-85,
https://doi.org/10.1016/j.biopha.2017.09.110 . .

TY  - JOUR
AU  - Stanisavljević, Suzana
AU  - Lukić, Jovanka
AU  - Momčilović, Miljana
AU  - Miljković, Marija
AU  - Jevtić, Bojan
AU  - Kojić, Milan
AU  - Golić, Nataša
AU  - Mostarica Stojković, Marija
AU  - Miljković, Đorđe
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6049
AB  - Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.
PB  - Wageningen Academic Publishers
T2  - Beneficial Microbes
T1  - Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis
IS  - 3
VL  - 7
DO  - 10.3920/BM2015.0159
SP  - 363
EP  - 373
ER  - 

@article{
author = "Stanisavljević, Suzana and Lukić, Jovanka and Momčilović, Miljana and Miljković, Marija and Jevtić, Bojan and Kojić, Milan and Golić, Nataša and Mostarica Stojković, Marija and Miljković, Đorđe",
year = "2016",
abstract = "Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.",
publisher = "Wageningen Academic Publishers",
journal = "Beneficial Microbes",
title = "Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis",
number = "3",
volume = "7",
doi = "10.3920/BM2015.0159",
pages = "363-373"
}

Stanisavljević, S., Lukić, J., Momčilović, M., Miljković, M., Jevtić, B., Kojić, M., Golić, N., Mostarica Stojković, M.,& Miljković, Đ.. (2016). Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis. in Beneficial Microbes
Wageningen Academic Publishers., 7(3), 363-373.
https://doi.org/10.3920/BM2015.0159

Stanisavljević S, Lukić J, Momčilović M, Miljković M, Jevtić B, Kojić M, Golić N, Mostarica Stojković M, Miljković Đ. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis. in Beneficial Microbes. 2016;7(3):363-373.
doi:10.3920/BM2015.0159 .

Stanisavljević, Suzana, Lukić, Jovanka, Momčilović, Miljana, Miljković, Marija, Jevtić, Bojan, Kojić, Milan, Golić, Nataša, Mostarica Stojković, Marija, Miljković, Đorđe, "Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis" in Beneficial Microbes, 7, no. 3 (2016):363-373,
https://doi.org/10.3920/BM2015.0159 . .

TY  - JOUR
AU  - Jevtić, Bojan
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Despotović, Jovana
AU  - Miljković, Đorđe
AU  - Timotijević, Gordana
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6050
AB  - Cucurbitacin E (CucE) is a highly oxidized steroid consisting of a tetracyclic triterpene. It is a member of a Cucurbitacin family of biomolecules that are predominantly found in Cucurbitaceae plants. CucE has already been identified as a potent anti-inflammatory compound. Here, its effects on CD4(+) T helper (Th) cells and macrophages, as the major encephalitogenic cells in the autoimmunity of the central nervous system, were investigated. Production of major pathogenic Th cell cytokines: interferon-gamma and interleukin-17 were inhibited under the influence of CucE. The effects of CucE on CD4(+) T cells were mediated through the modulation of aryl hydrocarbon receptor, STAT3, NFκB, p38 MAPK, and miR-146 signaling. Further, production of nitric oxide and reactive oxygen species, as well as phagocytic ability, were inhibited in macrophages treated with CucE. These results imply that CucE possesses powerful antiencephalitogenic activity.
PB  - American Chemical Society
T2  - Journal of Agricultural and Food Chemistry
T1  - Cucurbitacin E Potently Modulates the Activity of Encephalitogenic Cells
IS  - 24
VL  - 64
DO  - 10.1021/acs.jafc.6b00951
SP  - 4900
EP  - 4907
ER  - 

@article{
author = "Jevtić, Bojan and Nikolovski, Neda and Stanisavljević, Suzana and Despotović, Jovana and Miljković, Đorđe and Timotijević, Gordana",
year = "2016",
abstract = "Cucurbitacin E (CucE) is a highly oxidized steroid consisting of a tetracyclic triterpene. It is a member of a Cucurbitacin family of biomolecules that are predominantly found in Cucurbitaceae plants. CucE has already been identified as a potent anti-inflammatory compound. Here, its effects on CD4(+) T helper (Th) cells and macrophages, as the major encephalitogenic cells in the autoimmunity of the central nervous system, were investigated. Production of major pathogenic Th cell cytokines: interferon-gamma and interleukin-17 were inhibited under the influence of CucE. The effects of CucE on CD4(+) T cells were mediated through the modulation of aryl hydrocarbon receptor, STAT3, NFκB, p38 MAPK, and miR-146 signaling. Further, production of nitric oxide and reactive oxygen species, as well as phagocytic ability, were inhibited in macrophages treated with CucE. These results imply that CucE possesses powerful antiencephalitogenic activity.",
publisher = "American Chemical Society",
journal = "Journal of Agricultural and Food Chemistry",
title = "Cucurbitacin E Potently Modulates the Activity of Encephalitogenic Cells",
number = "24",
volume = "64",
doi = "10.1021/acs.jafc.6b00951",
pages = "4900-4907"
}

Jevtić, B., Nikolovski, N., Stanisavljević, S., Despotović, J., Miljković, Đ.,& Timotijević, G.. (2016). Cucurbitacin E Potently Modulates the Activity of Encephalitogenic Cells. in Journal of Agricultural and Food Chemistry
American Chemical Society., 64(24), 4900-4907.
https://doi.org/10.1021/acs.jafc.6b00951

Jevtić B, Nikolovski N, Stanisavljević S, Despotović J, Miljković Đ, Timotijević G. Cucurbitacin E Potently Modulates the Activity of Encephalitogenic Cells. in Journal of Agricultural and Food Chemistry. 2016;64(24):4900-4907.
doi:10.1021/acs.jafc.6b00951 .

Jevtić, Bojan, Nikolovski, Neda, Stanisavljević, Suzana, Despotović, Jovana, Miljković, Đorđe, Timotijević, Gordana, "Cucurbitacin E Potently Modulates the Activity of Encephalitogenic Cells" in Journal of Agricultural and Food Chemistry, 64, no. 24 (2016):4900-4907,
https://doi.org/10.1021/acs.jafc.6b00951 . .