TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sérgio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2112
AB  - Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T reg- ulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for mod- ulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry. Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice.
Conclusion: C43 can modulate the immune response through the intestine by promoting the im- munosuppressive Treg population.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut
EP  - 38
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2112
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sérgio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana",
year = "2023",
abstract = "Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T reg- ulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for mod- ulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry. Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice.
Conclusion: C43 can modulate the immune response through the intestine by promoting the im- munosuppressive Treg population.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut",
pages = "38-38",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2112"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I.. (2023). Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 38-38.
https://hdl.handle.net/21.15107/rcub_imagine_2112

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović I. Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:38-38.
https://hdl.handle.net/21.15107/rcub_imagine_2112 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sérgio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana, "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):38-38,
https://hdl.handle.net/21.15107/rcub_imagine_2112 .

TY  - JOUR
AU  - Gajić, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Šenerović, Lidija
AU  - Morić, Ivana
AU  - Šavikin, Katarina
AU  - Menković, Nebojša
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1638
AB  - Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiation in vitro. When applied orally to healthy mice, CE increased the proportion of CD11c+ dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingested Listeria monocytogenes as evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b+ macrophages and CD8+ cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86+ macrophages (CD11b+) and dendritic cells (CD11c+) was also enhanced in CE-pretreated infected mice. Further, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and the similar results were obtained in peritoneal macrophages in vitro. This effect of CE was associated with increased phosphorylation of IκB and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection with Listeria monocytogenes predominantly through increased activity of myeloid cells in the gut and in the spleen.
PB  - United Kingdom : Royal Society of Chemistry
T2  - Food and Function
T1  - Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice
EP  - 7803
IS  - 9
SP  - 7793
VL  - 11
DO  - 10.1039/D0FO00946F
ER  - 

@article{
author = "Gajić, Dragica and Saksida, Tamara and Koprivica, Ivan and Šenerović, Lidija and Morić, Ivana and Šavikin, Katarina and Menković, Nebojša and Pejnović, Nada and Stojanović, Ivana D.",
year = "2020",
abstract = "Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiation in vitro. When applied orally to healthy mice, CE increased the proportion of CD11c+ dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingested Listeria monocytogenes as evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b+ macrophages and CD8+ cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86+ macrophages (CD11b+) and dendritic cells (CD11c+) was also enhanced in CE-pretreated infected mice. Further, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and the similar results were obtained in peritoneal macrophages in vitro. This effect of CE was associated with increased phosphorylation of IκB and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection with Listeria monocytogenes predominantly through increased activity of myeloid cells in the gut and in the spleen.",
publisher = "United Kingdom : Royal Society of Chemistry",
journal = "Food and Function",
title = "Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice",
pages = "7803-7793",
number = "9",
volume = "11",
doi = "10.1039/D0FO00946F"
}

Gajić, D., Saksida, T., Koprivica, I., Šenerović, L., Morić, I., Šavikin, K., Menković, N., Pejnović, N.,& Stojanović, I. D.. (2020). Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice. in Food and Function
United Kingdom : Royal Society of Chemistry., 11(9), 7793-7803.
https://doi.org/10.1039/D0FO00946F

Gajić D, Saksida T, Koprivica I, Šenerović L, Morić I, Šavikin K, Menković N, Pejnović N, Stojanović ID. Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice. in Food and Function. 2020;11(9):7793-7803.
doi:10.1039/D0FO00946F .

Gajić, Dragica, Saksida, Tamara, Koprivica, Ivan, Šenerović, Lidija, Morić, Ivana, Šavikin, Katarina, Menković, Nebojša, Pejnović, Nada, Stojanović, Ivana D., "Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice" in Food and Function, 11, no. 9 (2020):7793-7803,
https://doi.org/10.1039/D0FO00946F . .

TY  - JOUR
AU  - Gajić, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Šenerović, Lidija
AU  - Morić, Ivana
AU  - Savikin, Katarina
AU  - Menković, Nebojša
AU  - Pejnović, Nada
AU  - Stojanović, Ivana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1366
AB  - Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiationin vitro. When applied orally to healthy mice, CE increased the proportion of CD11c(+)dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingestedListeria monocytogenesas evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b(+)macrophages and CD8(+)cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86(+)macrophages (CD11b(+)) and dendritic cells (CD11c(+)) were also enhanced in CE-pretreated infected mice. Furthermore, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and similar results were obtained in peritoneal macrophagesin vitro. This effect of CE was associated with increased phosphorylation of I kappa B and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection withL. monocytogenespredominantly through increased activity of myeloid cells in the gut and in the spleen.
PB  - Royal Soc Chemistry, Cambridge
T2  - Food & Function
T1  - Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice
EP  - 7803
IS  - 9
SP  - 7793
VL  - 11
DO  - 10.1039/d0fo00946f
ER  - 

@article{
author = "Gajić, Dragica and Saksida, Tamara and Koprivica, Ivan and Šenerović, Lidija and Morić, Ivana and Savikin, Katarina and Menković, Nebojša and Pejnović, Nada and Stojanović, Ivana",
year = "2020",
abstract = "Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiationin vitro. When applied orally to healthy mice, CE increased the proportion of CD11c(+)dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingestedListeria monocytogenesas evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b(+)macrophages and CD8(+)cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86(+)macrophages (CD11b(+)) and dendritic cells (CD11c(+)) were also enhanced in CE-pretreated infected mice. Furthermore, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and similar results were obtained in peritoneal macrophagesin vitro. This effect of CE was associated with increased phosphorylation of I kappa B and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection withL. monocytogenespredominantly through increased activity of myeloid cells in the gut and in the spleen.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Food & Function",
title = "Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice",
pages = "7803-7793",
number = "9",
volume = "11",
doi = "10.1039/d0fo00946f"
}

Gajić, D., Saksida, T., Koprivica, I., Šenerović, L., Morić, I., Savikin, K., Menković, N., Pejnović, N.,& Stojanović, I.. (2020). Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice. in Food & Function
Royal Soc Chemistry, Cambridge., 11(9), 7793-7803.
https://doi.org/10.1039/d0fo00946f

Gajić D, Saksida T, Koprivica I, Šenerović L, Morić I, Savikin K, Menković N, Pejnović N, Stojanović I. Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice. in Food & Function. 2020;11(9):7793-7803.
doi:10.1039/d0fo00946f .

Gajić, Dragica, Saksida, Tamara, Koprivica, Ivan, Šenerović, Lidija, Morić, Ivana, Savikin, Katarina, Menković, Nebojša, Pejnović, Nada, Stojanović, Ivana, "Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice" in Food & Function, 11, no. 9 (2020):7793-7803,
https://doi.org/10.1039/d0fo00946f . .

TY  - JOUR
AU  - Vujicić, Milica
AU  - Saksida, Tamara
AU  - Despotović, Sanja
AU  - Soković Bajić, Svetlana
AU  - Lalić, Ivana
AU  - Koprivica, Ivan
AU  - Gajić, Dragica
AU  - Golić, Nataša
AU  - Tolinački, Maja
AU  - Stojanović, Ivana
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1182
AB  - Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-gamma in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier
VL  - 8
DO  - 10.1038/s41598-018-24706-3
ER  - 

@article{
author = "Vujicić, Milica and Saksida, Tamara and Despotović, Sanja and Soković Bajić, Svetlana and Lalić, Ivana and Koprivica, Ivan and Gajić, Dragica and Golić, Nataša and Tolinački, Maja and Stojanović, Ivana",
year = "2018",
abstract = "Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-gamma in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier",
volume = "8",
doi = "10.1038/s41598-018-24706-3"
}

Vujicić, M., Saksida, T., Despotović, S., Soković Bajić, S., Lalić, I., Koprivica, I., Gajić, D., Golić, N., Tolinački, M.,& Stojanović, I.. (2018). The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier. in Scientific Reports
Nature Publishing Group, London., 8.
https://doi.org/10.1038/s41598-018-24706-3

Vujicić M, Saksida T, Despotović S, Soković Bajić S, Lalić I, Koprivica I, Gajić D, Golić N, Tolinački M, Stojanović I. The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier. in Scientific Reports. 2018;8.
doi:10.1038/s41598-018-24706-3 .

Vujicić, Milica, Saksida, Tamara, Despotović, Sanja, Soković Bajić, Svetlana, Lalić, Ivana, Koprivica, Ivan, Gajić, Dragica, Golić, Nataša, Tolinački, Maja, Stojanović, Ivana, "The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier" in Scientific Reports, 8 (2018),
https://doi.org/10.1038/s41598-018-24706-3 . .