125 results on '"Hauk, Vanesa"'
Search Results
2. Vasoactive intestinal peptide induces metabolic rewiring of human-derived cytotrophoblast cells to promote cell migration
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Merech, Fátima, Lara, Brenda, Rios, Daiana, Paparini, Daniel, Ramhorst, Rosanna, Hauk, Vanesa, Pérez Leirós, Claudia, and Vota, Daiana
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- 2025
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3. VPAC1 and VPAC2 receptor deficiencies negatively influence pregnancy outcome through distinct and overlapping modulations of immune, trophoblast and vascular functions
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Calo, Guillermina, Hauk, Vanesa, Vota, Daiana, Van, Christina, Condro, Michael, Gallino, Lucila, Ramhorst, Rosanna, Waschek, James, and Pérez Leirós, Claudia
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- 2023
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4. Vasoactive intestinal peptide deficiency promotes ovarian dysfunction associated to a proinflammatory microenvironment reminiscent of premature aging
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Gallino, Lucila, Hauk, Vanesa, Castagnola, Lara, Vota, Daiana, Pascuali, Natalia, Parborell, Fernanda, May, Maria, Fontana, Vanina, Merech, Fatima, Naguila, Zaira, Waschek, James, Leirós, Claudia Perez, and Ramhorst, Rosanna
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- 2023
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5. SARS-CoV-2 infection negatively affects ovarian function in ART patients
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Herrero, Yamila, Pascuali, Natalia, Velázquez, Candela, Oubiña, Gonzalo, Hauk, Vanesa, de Zúñiga, Ignacio, Peña, Mariana Gómez, Martínez, Gustavo, Lavolpe, Mariano, Veiga, Florencia, Neuspiller, Fernando, Abramovich, Dalhia, Scotti, Leopoldina, and Parborell, Fernanda
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- 2022
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6. Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits
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Allo, Verónica C. Martínez, Hauk, Vanesa, Sarbia, Nicolas, Pinto, Nicolás A., Croci, Diego O., Dalotto-Moreno, Tomás, Morales, Rosa M., Gatto, Sabrina G., Cocco, Montana N. Manselle, Stupirski, Juan C., Deladoey, Ángel, Maronna, Esteban, Marcaida, Priscila, Durigan, Virginia, Secco, Anastasia, Mamani, Marta, Dos Santos, Alicia, Pellet, Antonio Catalán, Leiros, Claudia Pérez, Rabinovich, Gabriel A., and Toscano, Marta A.
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- 2020
7. Growth impairment, increased placental glucose uptake and altered transplacental transport in VIP deficient pregnancies: Maternal vs. placental contributions
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Merech, Fátima, Hauk, Vanesa, Paparini, Daniel, Fernandez, Laura, Naguila, Zaira, Ramhorst, Rosanna, Waschek, James, Pérez Leirós, Claudia, and Vota, Daiana
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- 2021
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8. Progesterone and VIP cross-talk enhances phagocytosis and anti-inflammatory profile in trophoblast-derived cells
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Vota, Daiana, Aguero, Mariana, Grasso, Esteban, Hauk, Vanesa, Gallino, Lucila, Soczewski, Elizabeth, Pérez Leirós, Claudia, and Ramhorst, Rosanna
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- 2017
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9. Monocyte immunometabolic reprogramming in human pregnancy: contribution of trophoblast cells.
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Merech, Fátima, Gori, Soledad, Calo, Guillermina, Hauk, Vanesa, Paparini, Daniel, Rios, Daiana, Lara, Brenda, Doga, Luciana, D'Eramo, Luciana, Squassi, Aldo, Ramhorst, Rosanna, Argüello, Rafael J., Leirós, Claudia Pérez, and Vota, Daiana
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TROPHOBLAST ,CELL physiology ,PREGNANCY ,PREGNANT women ,MONOCYTES ,HUMAN phenotype - Abstract
Immunometabolism research is uncovering the relationship between metabolic features and immune cell functions in physiological and pathological conditions. Normal pregnancy entails a fine immune and metabolic regulation of the maternal-fetal interaction to assist the energetic demands of the fetus with immune homeostasis maintenance. Here, we determined the immunometabolic status of monocytes of pregnant women compared with nonpregnant controls and its impact on monocyte anti-inflammatory functions such as efferocytosis. Monocytes from pregnant women (16-20 wk) and nonpregnant age-matched controls were studied. Single cell-based metabolic assays using freshly isolated monocytes from both groups were carried out in parallel with functional assays ex vivo to evaluate monocyte efferocytic capacity. On the other hand, various in vitro metabolic assays with human monocytes or monocyte-derived macrophages were designed to explore the effect of trophoblast cells in the profiles observed. We found that pregnancy alters monocyte metabolism and function. An increased glucose dependency and enhanced efferocytosis were detected in monocytes from pregnant women at resting states, compared with nonpregnant controls. Furthermore, monocytes display a reduced glycolytic response when stimulated with lipopolysaccharide (LPS). The metabolic profiling of monocytes at this stage of pregnancy was comparable with the immunometabolic phenotypes of human monocytes treated in vitro with human first trimester trophoblast cell conditioned media. These findings suggest that immunometabolic mechanisms are involved in the functional shaping of monocytes during pregnancy with a contribution of trophoblast cells. Results provide new clues for future hypotheses regarding pregnancies complicated by metabolic disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Porphyromonas gingivalis outer membrane vesicles shape trophoblast cell metabolism impairing functions associated to adverse pregnancy outcome.
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Lara, Brenda, Loureiro, Iñaki, Gliosca, Laura, Castagnola, Lara, Merech, Fátima, Gallino, Lucila, Calo, Guillermina, Sassot, Matías, Ramhorst, Rosanna, Vota, Daiana, Pérez Leirós, Claudia, and Hauk, Vanesa
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TROPHOBLAST ,PREGNANCY outcomes ,EXTRACELLULAR vesicles ,PORPHYROMONAS gingivalis ,CELL morphology ,CELL metabolism - Abstract
Periodontitis is proposed as a risk factor for preterm delivery, fetal growth restriction, and preeclampsia with severe consequences for maternal and neonatal health, but the biological mechanisms involved are elusive. Porphyromonas gingivalis gain access to the placental bed and impair trophoblast cell function, as assessed in murine and human pregnancy, suggesting a pathogenic role in adverse pregnancy and neonatal outcomes. P. gingivalis releases outer membrane vesicles (P. gingivalis OMV) during growth that spread to distant tissues and are internalized in host cells as described in metabolic, neurological, and vascular systemic diseases. Here we tested the hypothesis that P. gingivalis OMV internalized in trophoblast cells disrupt their metabolism leading to trophoblast and placenta dysfunction and adverse pregnancy outcomes. An in vitro design with human trophoblast cells incubated with P. gingivalis OMV was used together with ex vivo and in vivo approaches in pregnant mice treated with P. gingivalis OMV. P. gingivalis OMV modulated human trophoblast cell metabolism by reducing glycolytic pathways and decreasing total reactive oxygen species with sustained mitochondrial activity. Metabolic changes induced by P. gingivalis OMV did not compromise cell viability; instead, it turned trophoblast cells into a metabolic resting state where central functions such as migration and invasion were reduced. The effects of P. gingivalis OMV on human trophoblast cells were corroborated ex vivo in mouse whole placenta and in vivo in pregnant mice: P. gingivalis OMV reduced glycolytic pathways in the placenta and led to lower placental and fetal weight gain in vivo with reduced placental expression of the glucose transporter GLUT1. The present results point to OMV as a key component of P. gingivalis involved in adverse pregnancy outcomes, and even more, unveil a metabolic cue in the deleterious effect of P. gingivalis OMV on trophoblast cells and mouse pregnancy, providing new clues to understand pathogenic mechanisms in pregnancy complications and other systemic diseases. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Anti-tissue transglutaminase antibody inhibits apoptotic cell clearance by macrophages in pregnant NOD mice
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Sóñora, Cecilia, Mourglia-Ettlin, Gustavo, Calo, Guillermina, Hauk, Vanesa, Ramhorst, Rosanna, Hernández, Ana, and Leirós, Claudia Pérez
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- 2014
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12. Extracellular Vesicles of Porphyromonas gingivalis Disrupt Trophoblast Cell Interaction with Vascular and Immune Cells in an In Vitro Model of Early Placentation.
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Lara, Brenda, Sassot, Matías, Calo, Guillermina, Paparini, Daniel, Gliosca, Laura, Chaufan, Gabriela, Loureiro, Iñaki, Vota, Daiana, Ramhorst, Rosanna, Pérez Leirós, Claudia, and Hauk, Vanesa
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TROPHOBLAST ,EXTRACELLULAR vesicles ,PORPHYROMONAS gingivalis ,PORPHYROMONAS gingivalis infections ,PREGNANCY outcomes ,ALZHEIMER'S disease - Abstract
Extracellular vesicles released by the primary pathogen of periodontal disease Porphyromonas gingivalis (Pg), referred to as outer membrane vesicles (OMVs), have been associated with the pathogenesis of systemic diseases like cardiovascular disease, rheumatoid arthritis, and Alzheimer's disease. A pathogenic role for Pg by disrupting placental homeostasis was proposed in the association between periodontal disease and adverse pregnancy outcomes. On the basis that trophoblast-derived factors modulate endothelial and immune cell profiles in normal pregnancy and the scarce presence of Pg in placenta, we hypothesized that OMVs from Pg affect trophoblast cell phenotype, impairing trophoblast–endothelium and trophoblast–neutrophil interactions. By means of in vitro designs with first-trimester human trophoblast cells, endothelial cells, and freshly isolated neutrophils, we showed that Pg OMVs are internalized by trophoblast cells and modulate the activity and expression of functional markers. Trophoblast cells primed with Pg OMVs enhanced neutrophil chemoattraction and lost their anti-inflammatory effect. In addition, reduced migration with enhanced adhesion of monocytes was found in endothelial cells upon incubation with the media from trophoblast cells pretreated with Pg OMVs. Taken together, the results support a pathogenic role of Pg OMVs at early stages of pregnancy and placentation through disruption of trophoblast contribution to vascular transformation and immune homeostasis maintenance. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Modulation of macrophage inflammatory profile in pregnant nonobese diabetic (NOD) mice
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Larocca, Luciana, Hauk, Vanesa, Calafat, Mario, Roca, Valeria, Fraccaroli, Laura, Franchi, Ana, Ramhorst, Rosanna, and Leirós, Claudia Pérez
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- 2011
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14. Targeting first trimester trophoblast cell metabolism modulates its susceptibility to Zika virus infection.
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Kafer, Diego, Marquez, Agostina, Merech, Fátima, Hauk, Vanesa, Paparini, Daniel, Ramhorst, Rosanna, Leirós, Claudia Pérez, Garcia, Cybele, and Vota, Daiana
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ZIKA virus infections ,TROPHOBLAST ,CELL metabolism ,VASOACTIVE intestinal peptide ,UNSATURATED fatty acids ,ZIKA virus - Abstract
In the last 15 years Zika virus (ZIKV) caused several outbreaks of increasing scale in Micronesia, South Pacific islands, and more recently in the Caribbean and South America. The severity of the clinical presentation in neonates from pregnant women infected with ZIKV during the last outbreak supports the relevance of unraveling the mechanism of infection and viral persistence in the placenta with local viral isolates. Here, we investigated the relevance of trophoblast metabolic rewiring for viral multiplication and the role of the vasoactive intestinal peptide (VIP) as an endogenous factor associated with placental restriction to ZIKV infection at early pregnancy. Our in vitro model demonstrated that ZIKV triggers metabolic rewiring in first trimester cytotrophoblast‐derived cells by increasing glucose utilization as fuel to sustain its replication, decreasing long‐chain polyunsaturated fatty acid uptake, and promoting lipid droplets accumulation to favor its multiplication. Of note, variations in nutrient availability modulated viral spread in trophoblast cultures. The presence of VIP during trophoblast infection impaired ZIKV infective particle production and viral replication, restoring cell migration and metabolism. Moreover, the blockade of endogenous VIP signaling increased viral particle production and the viral entry receptor AXL expression. These results highlight the potential role of VIP as an endogenous antiviral factor related to trophoblast cell permissiveness to ZIKV infection at early pregnancy. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal–placental interaction
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Paparini, Daniel, Grasso, Esteban, Calo, Guillermina, Vota, Daiana, Hauk, Vanesa, Ramhorst, Rosanna, and Pérez Leirós, Claudia
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- 2015
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16. Vasoactive Intestinal Peptide Induces an Immunosuppressant Microenvironment in the Maternal–Fetal Interface of Non-Obese Diabetic Mice and Improves Early Pregnancy Outcome
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Hauk, Vanesa, Azzam, Sofía, Calo, Guillermina, Gallino, Lucila, Paparini, Daniel, Franchi, Ana, Ramhorst, Rosanna, and Leirós, Claudia Pérez
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- 2014
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17. From decidualization to pregnancy progression: An overview of immune and metabolic effects of VIP.
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Ramhorst, Rosanna, Grasso, Esteban, Vota, Daiana, Gori, Soledad, Hauk, Vanesa, Paparini, Daniel, Calo, Guillermina, and Pérez Leirós, Claudia
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EMBRYO implantation ,VASOACTIVE intestinal peptide ,CELL physiology ,PREGNANCY ,NEONATOLOGY ,RECURRENT miscarriage - Abstract
Background: A tight immune and metabolic regulation underlies the early maternal‐placental interaction to assist the energetic dynamic demands of the fetus throughout pregnancy. The vasoactive intestinal peptide (VIP) holds biochemical, metabolic and immune properties consistent with a regulatory role during pregnancy. Aim: Here we overview critical aspects of embryo implantation and placental development with special focus on the immune and metabolic effects of VIP expressed by decidual and trophoblast cells. Content: During decidualization, endometrial stromal cells undergo reticular stress and trigger unfolded protein response (UPR) that enable expansion of their endoplasmic reticulum and immunomodulatory factor synthesis. These processes appear differentially affected in recurrent abortion and in vitro fertilization failure suggesting their relevance in reproductive pathologies. Similarly, defective placentation associates with altered immune, vascular and trophoblast interaction resulting in complicated pregnancies that threaten maternal and neonatal health and underlie metabolic programming of adult life. We discuss the most recent research on decidual, trophoblast and immune cell interaction on the light of VIP regulation. Its role in decidualization and UPR associated with a sterile inflammatory response and angiogenesis is discussed. Evidence on VIP modulation of cytotrophoblast cell function, metabolism and immune profile is revised as well as the shaping of decidual leukocyte phenotype and function from decidualization to term. Implications: The broad spectrum of effects of VIP from implantation to term in normal and pathological conditions summarized here might contribute to the identification of novel biomarkers for diagnosis and pharmacological targeting. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Gingival crevicular fluid from pregnant women impairs trophoblast cell function and trophoblast‐neutrophil interaction.
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Hauk, Vanesa, D'Eramo, Luciana, Calo, Guillermina, Merech, Fátima, Doga, Luciana, Lara, Brenda, Gliosca, Laura, Massone, Carla, Molgatini, Susana, Ramhorst, Rosanna, Squassi, Aldo, and Pérez Leirós, Claudia
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CELL physiology , *GINGIVAL fluid , *PREGNANT women , *TROPHOBLAST , *PERIODONTITIS , *PREGNANCY complications - Abstract
Problem: A strong association between periodontitis and higher susceptibility to pregnancy complications like preeclampsia has been reported although the mechanisms remain elusive. Trophoblast cells modulate the recruitment and functional shaping of maternal leukocytes at early stages to sustain an antiinflammatory microenvironment and fetal growth. Neutrophil activation with reactive oxygen species (ROS) release is associated with preeclampsia. Our aim was to study the effect of the gingival crevicular fluid (GCF) from pregnant women on trophoblast cell function and trophoblast‐neutrophil interaction. Method of study: Pregnant women at 16–20 weeks of gestation (n = 27) and non‐pregnant women (n = 8) as the control group were studied for gingivoperiodontal clinical score evaluation and GCF collection. Total bacteria and common periodontal pathogens were analyzed in GCF samples. The effect of each GCF sample was tested on first trimester trophoblast‐derived cells to assess cell migration, cytokine expression and glucose uptake. Also, the effect of GCF on human peripheral neutrophil chemoattraction by trophoblast cells and ROS formation was assessed. Results: Gingival crevicular fluid from pregnant women reduced trophoblast cell migration, increased proinflammatory marker expression and glucose uptake. A significant correlation between gingivoperiodontal score and trophoblast dysfunction was observed. Upon conditioning of trophoblast cells with GCF, only the GCF from pregnant women stimulated neutrophil chemoattraction. Similarly, GCF from pregnant but not from non‐pregnant controls stimulated ROS formation in neutrophils. Conclusions: Gingival crevicular fluid from pregnant women is deleterious for first trimester trophoblast cell function. These effects could lead to placental homeostasis disruption underlying a pathogenic mechanism of pregnancy complications associated to periodontal disease. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Trend: A test for recurrent implantation failure patients' detection by qPCR array.
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Grasso, Esteban, Marcial, Agustina, Gori, Soledad, Hauk, Vanesa, Castagnola, Lara, Irigoyen, Marcela, Cattaneo, Antonio, Gnocchi, Diego, Tessari, Lautaro, Pisanelli, María Laura, Leirós, Claudia Pérez, and Ramhorst, Rosanna
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- 2024
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20. Control of the inflammatory response during pregnancy: Potential role of VIP as a regulatory peptide
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Ramhorst, Rosanna Elizabeth, Calo, Guillermina, Paparini, Daniel Esteban, Vota, Daiana Marina, Hauk, Vanesa Cintia, Gallino, Lucila, Merech, Fátima Isabel, Grasso, Esteban Nicolas, and Perez Leiros, Claudia
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Medicina Básica ,PREGNANCY ,CIENCIAS MÉDICAS Y DE LA SALUD ,VASOACTIVE INTESTINAL POLYPEPTIDE ,TROPHOBLAST CELL LINES ,IMMUNE HOMEOSTASIS ,Inmunología - Abstract
A network of cell–cell communications through contact and soluble factors supports the maternal–placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti-inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast–immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation. Fil: Ramhorst, Rosanna Elizabeth. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Calo, Guillermina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Paparini, Daniel Esteban. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Vota, Daiana Marina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Hauk, Vanesa Cintia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gallino, Lucila. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Merech, Fatima. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Perez Leiros, Claudia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
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- 2019
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21. Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period.
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Fernández, Laura, Grasso, Esteban, Soczewski, Elizabeth, Gori, Soledad, Calo, Guillermina, Hauk, Vanesa, Sabbione, Florencia, Gallino, Lucila, Martínez, Gustavo, Irigoyen, Marcela, Bestach, Yesica, Pérez Leirós, Claudia, and Ramhorst, Rosanna
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HUMAN embryos ,NATURAL selection ,REGULATORY T cells ,INFLAMMATION ,BLASTOCYST - Abstract
Problem: Decidualized cells display an active role during embryo implantation sensing blastocyst quality, allowing the implantation of normal developed blastocysts and preventing the invasion of impaired developed ones. Here, we characterized the immune microenvironment generated by decidualized cells in response to soluble factors secreted by blastocysts that shape the receptive milieu. Method of Study: We used an in vitro model of decidualization based on the Human Endometrial Stromal Cells line (HESC) differentiated with medroxiprogesterone and dibutyryl‐cAMP, then treated with human blastocysts‐conditioned media (BCM) classified according to their quality. Results: Decidualized cells treated with BCM from impaired developed blastocysts increased IL‐1β production. Next, we evaluated the ability of decidualized cells to modulate other mediators associated with menstruation as chemokines. Decidualized cells responded to stimulation with BCM from impaired developed blastocysts increasing CXCL12 expression and CXCL8 secretion. The modulation of these markers was associated with the recruitment and activation of neutrophils, while regulatory T cells recruitment was restrained. These changes were not observed in the presence of BCM from normal developed blastocysts. Conclusion: Soluble factors released by impaired developed blastocysts induce an exacerbated inflammatory response associated with neutrophils recruitment and activation, providing new clues to understand the molecular basis of the embryo‐endometrial dialogue. [ABSTRACT FROM AUTHOR]
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- 2022
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22. Oral infections and pregnancy outcome: Outer membrane vesicles from porphyromonas gingivalis impair trophoblast cell function
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Lara, Brenda, Merech, Fátima, Calo, Guillermina, Gliosca, Laura, Vota, Daiana, Ramhorst, Rosanna, Leirós, Claudia Pérez, and Hauk, Vanesa
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- 2022
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23. Zika virus alters trophoblast metabolism and apoptotic signaling pathways to promote viral propagation and persistence in the placenta at early pregnancy
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Kafer, Diego, Marquez, Agostina, Paparini, Daniel, Hauk, Vanesa, Merech, Fátima, Ramhorst, Rosanna, Leirós, Claudia Pérez, García, Cybele, and Vota, Daiana
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- 2022
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24. Extracellular vesicles of first trimester trophoblast cell line overexpressing VPAC2 induce anti-inflammatory signals in HB cell and maternal monocytes
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Paparini, Daniel E., Grasso, Esteban N., Vota, Daiana, Hauk, Vanesa, Merech, Fátima, Lara, Brenda, Izbizky, Gustavo, Abasolo, Juan Ignacio, Ramhorst, Rosanna, and Leirós, Claudia Pérez
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- 2022
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25. Zika virus infection of first trimester trophoblast cells affects cell migration, metabolism and immune homeostasis control.
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Vota, Daiana, Torti, María, Paparini, Daniel, Giovannoni, Federico, Merech, Fátima, Hauk, Vanesa, Calo, Guillermina, Ramhorst, Rosanna, Garcia, Cybele, and Pérez Leirós, Claudia
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ZIKA virus infections ,TROPHOBLAST ,BRAIN-derived neurotrophic factor ,CELL migration ,MATERNAL-fetal exchange ,FETAL growth retardation ,VASOACTIVE intestinal peptide - Abstract
Zika virus (ZIKV) re‐emerged after circulating almost undetected for many years and the last spread in 2015 was the major outbreak reported. ZIKV infection was associated with congenital fetal growth anomalies such as microcephaly, brain calcifications, and low birth weight related to fetal growth restriction. In this study, we investigated the effect of ZIKV infection on first trimester trophoblast cell function and metabolism. We also studied the interaction of trophoblast cells with decidual immune populations. Results presented here demonstrate that ZIKV infection triggered a strong antiviral response in first trimester cytotrophoblast‐derived cells, impaired cell migration, increased glucose uptake and GLUT3 expression, and reduced brain derived neurotrophic factor (BDNF) expression. ZIKV infection also conditioned trophoblast cells to favor a tolerogenic response since an increased recruitment of CD14+ monocytes bearing an anti‐inflammatory profile, increased CD4+ T cells and NK CD56Dim and NK CD56Bright populations and an increment in the population CD4+ FOXP3+ IL‐10+ cells was observed. Interestingly, when ZIKV infection of trophoblast cells occurred in the presence of the vasoactive intestinal peptide (VIP) there was lower detection of viral RNA and reduced toll‐like receptor‐3 and viperin messenger RNA expression, along with reduced CD56Dim cells trafficking to trophoblast conditioned media. The effects of ZIKV infection on trophoblast cell function and immune‐trophoblast interaction shown here could contribute to defective placentation and ZIKV persistence at the fetal‐maternal interface. The inhibitory effect of VIP on ZIKV infection of trophoblast cells highlights its potential as a candidate molecule to interfere ZIKV infection during early pregnancy. [ABSTRACT FROM AUTHOR]
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- 2021
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26. Decidual factors and vasoactive intestinal peptide guide monocytes to higher migration, efferocytosis and wound healing in term human pregnancy.
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Paparini, Daniel Esteban, Grasso, Esteban, Fernandez, Laura del Carmen, Merech, Fátima, Weingrill‐Barbano, Rodrigo, Correa‐Silva, Simone, Izbizky, Gustavo, Abasolo, José Ignacio, Hauk, Vanesa, Ramhorst, Rosanna, Bevilaqcua, Estela, and Pérez Leirós, Claudia
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VASOACTIVE intestinal peptide ,MONOCYTES ,HEALING ,HOMEOSTASIS ,WOUND healing - Abstract
Aim: To explore the functional profile of circulating monocytes and decidual macrophages at term human pregnancy and their contribution to tissue repair upon stimulation ex vivo with decidual factors and the vasoactive intestinal peptide (VIP). Methods: Peripheral blood monocytes were isolated from pregnant and non‐pregnant volunteers and tested in vitro with decidual explants from term placenta and VIP. The effect of VIP on decidual explants and the effect of its conditioned media on monocytes or decidual macrophages isolated by magnetic beads was carried out by RT‐qPCR and ELISA for cytokines expression and release. Migration assays were performed in transwell systems. Efferocytosis was assessed in monocytes or decidual macrophages with CFSE‐labelled autologous apoptotic neutrophils and quantified by flow cytometry. Monocyte and decidual macrophages wound healing capacity was evaluated using human endometrial stromal cell monolayers. Immunohistochemistry was performed in serial tissue sections of different placentas. Results: VIP is expressed in the villi as well as in trophoblast giant cells distributed within the decidua of term placenta. VIP induced the expression of antiinflmammatory markers and monocyte chemoattractant CCL2 and CCL3 in decidual tissues. Monocytes presented higher migration towards decidual explants than CD4 and CD8 cells. VIP‐conditioned monocytes displayed an enhanced efferocytosis and wound healing capacity comparable to that of decidual macrophages. Moreover limited efferocytosis of pregnant women monocytes was restored by VIP‐induced decidual factors. Conclusion: Results show the conditioning of monocytes by decidual factors and VIP to sustain processes required for tissue repair and homeostasis maintenance in term placenta. [ABSTRACT FROM AUTHOR]
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- 2021
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27. Immunoregulation of the decidualization program: focus on the endoplasmic reticulum stress.
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Soczewski, Elizabeth, Grasso, Esteban, Gallino, Lucila, Hauk, Vanesa, Fernández, Laura, Gori, Soledad, Paparini, Daniel, Perez Leirós, Claudia, and Ramhorst, Rosanna
- Subjects
ENDOPLASMIC reticulum ,RECURRENT miscarriage ,EMBRYO implantation ,PREGNANCY complications ,IMMUNOREGULATION - Abstract
Decidualization denotes the reprogramming of endometrial stromal cells that includes the secretion of different mediators like cytokines, chemokines, and the selective recruitment of immune cells. This physiological process involves changes in the secretome of the endometrial stromal cells leading to the production of immunomodulatory factors. The increased amount of protein secretion is associated with a physiological endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR), allowing the expansion of ER and the machinery to assist the protein folding. Notably, the signaling pathways involved in the ER stress and the UPR are interconnected with the onset of a sterile inflammatory response, as well as with angiogenesis. Both of these processes have a key role in decidualization and placentation, therefore, alterations in them could lead to pregnancy complications. In this review, we will discuss how the induction of ER stress and the UPR processes that accompanies the decidualization are associated with embryo implantation and whether they might condition pregnancy outcome. The ER stress activates/triggers sensing proteins which, among others, induces kinase/RNAse-TXNIP expression, activating the NLRP3 inflammasome. This multiprotein system allows caspase-1 activation, which catalyzes the cleavage of the inactive IL-1β proform toward the mature secretory form, with pro-implantatory effects. However, the sterile inflammatory response should be later controlled in favor of a tolerogenic microenvironment to sustain pregnancy. In accordance, alterations of the ER stress and UPR processes can be reflected in recurrent implantation failures (RIF), recurrent pregnancy loss (RPL), or complications associated with deficient placentation, such as preeclampsia (PE). [ABSTRACT FROM AUTHOR]
- Published
- 2020
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28. VIP Promotes Recruitment of Tregs to the Uterine–Placental Interface During the Peri-Implantation Period to Sustain a Tolerogenic Microenvironment.
- Author
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Gallino, Lucila, Hauk, Vanesa, Fernández, Laura, Soczewski, Elizabeth, Gori, Soledad, Grasso, Esteban, Calo, Guillermina, Saraco, Nora, Berensztein, Esperanza, Waschek, James A., Pérez Leirós, Claudia, and Ramhorst, Rosanna
- Subjects
SUPPRESSOR cells ,VASCULAR endothelial growth factors ,TRANSFORMING growth factors ,VASOACTIVE intestinal peptide ,EMBRYO implantation - Abstract
Uterine receptivity and embryo implantation are two main processes that need a finely regulated balance between pro-inflammatory and tolerogenic mediators to allow a successful pregnancy. The neuroimmune peptide vasoactive intestinal peptide (VIP) is a key regulator, and it is involved in the induction of regulatory T cells (Tregs), which are crucial in both processes. Here, we analyzed the ability of endogenous and exogenous VIP to sustain a tolerogenic microenvironment during the peri-implantation period, particularly focusing on Treg recruitment. Wild-type (WT) and VIP-deficient mice [heterozygous (HT, +/−), knockout (KO, −/−)], and FOXP3-knock-in-GFP mice either pregnant or in estrus were used. During the day of estrus, we found significant histological differences between the uterus of WT mice vs. VIP-deficient mice, with the latter exhibiting undetectable levels of FOXP3 expression, decreased expression of interleukin (IL)-10, and vascular endothelial growth factor (VEGF)c, and increased gene expression of the Th17 proinflammatory transcription factor RORγt. To study the implantation window, we mated WT and VIP (+/−) females with WT males and observed altered FOXP3, VEGFc, IL-10, and transforming growth factor (TGF)β gene expression at the implantation sites at day 5.5 (d5.5), demonstrating a more inflammatory environment in VIP (+/−) vs. VIP (+/+) females. A similar molecular profile was observed at implantation sites of WT × WT mice treated with VIP antagonist at d3.5. We then examined the ability GFP-sorted CD4+ cells from FOXP3-GFP females to migrate toward conditioned media (CM) obtained from d5.5 implantation sites cultured in the absence/presence of VIP or VIP antagonist. VIP treatment increased CD4+FOXP3+ and decreased CD4+ total cell migration towards implantation sites, and VIP antagonist prevented these effects. Finally, we performed adoptive cell transfer of Tregs (sorted from FOXP3-GFP females) in VIP-deficient-mice, and we observed that FOXP3-GFP cells were mainly recruited into the uterus/implantation sites compared to all other tested tissues. In addition, after Treg transfer, we found an increase in IL-10 expression and VEGFc in HT females and allowed embryo implantation in KO females. In conclusion, VIP contributes to a local tolerogenic response necessary for successful pregnancy, preventing the development of a hostile uterine microenvironment for implantation by the selective recruitment of Tregs during the peri-implantation period. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
29. Vasoactive intestinal peptide shapes first-trimester placenta trophoblast, vascular, and immune cell cooperation.
- Author
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Paparini, Daniel E., Choudhury, Ruhul H., Vota, Daiana M., Karolczak‐Bayatti, Magdalena, Finn‐Sell, Sarah, Grasso, Esteban N., Hauk, Vanesa C., Ramhorst, Rosanna, Pérez Leirós, Claudia, Aplin, John D., Karolczak-Bayatti, Magdalena, and Finn-Sell, Sarah
- Subjects
TROPHOBLAST ,VASOACTIVE intestinal peptide ,PLACENTA ,PREGNANCY complications ,CELLS ,FETAL development ,BLASTOCYST ,RESEARCH ,FIRST trimester of pregnancy ,RESEARCH methodology ,MACROPHAGES ,KILLER cells ,EVALUATION research ,MEDICAL cooperation ,COMPARATIVE studies ,CELL lines - Abstract
Background and Purpose: Extravillous trophoblast (EVT) cells are responsible for decidual stromal invasion, vascular transformation, and the recruitment and functional modulation of maternal leukocytes in the first-trimester pregnant uterus. An early disruption of EVT function leads to placental insufficiency underlying pregnancy complications such as preeclampsia and fetal growth restriction. Vasoactive intestinal peptide (VIP) is a vasodilating and immune modulatory factor synthesized by trophoblast cells. However, its role in first-trimester placenta has not been explored. Here, we tested the hypothesis that VIP is involved in first-trimester EVT outgrowth, spiral artery remodelling, balancing angiogenesis, and maintenance of immune homeostasis.Experimental Approach: First-trimester placental tissue (five to nine weeks of gestation) was collected, and was used for EVT outgrowth experiments, immunofluorescence, isolation of decidual natural killer (dNK) cells and decidual macrophages (dMA), and functional assays. Peripheral blood monocytes were differentiated with GM-CSF and used for angiogenesis assays.Key Results: In decidua basalis, VIP+ EVT were observed sprouting from cell columns and lining spiral arterioles. EVT migrating from placental explants were also VIP+. VIP increased EVT outgrowth and IL-10 release, whereas it decreased pro-inflammatory cytokine production in EVT, dNK cells, and dMA. VIP disrupted endothelial cell networks, both directly and indirectly via an effect on macrophages.Conclusion and Implications: The results suggest that VIP assists the progress of EVT invasion and vessel remodelling in first-trimester placental bed in an immunologically "silent" milieu. The effects of VIP in the present ex vivo human placental model endorse its potential as a therapeutic candidate for deep placentation disorders. [ABSTRACT FROM AUTHOR]- Published
- 2019
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30. Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy outcome in mice.
- Author
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Hauk, Vanesa, Vota, Daiana, Gallino, Lucila, Calo, Guillermina, Paparini, Daniel, Merech, Fátima, Ochoa, Federico, Zotta, Elsa, Ramhorst, Rosanna, Waschek, James, and Leirós, Claudia Pérez
- Abstract
Immune homeostasis maintenance throughout pregnancy is critical for normal fetal development. Trophoblast cells differentiate into an invasive phenotype and contribute to the transformation of maternal arteries and the functional shaping of decidual leukocyte populations. Insufficient trophoblast invasion, inadequate vascular remodeling, and a loss of immunologic homeostasis are associated with pregnancy complications, such as preeclampsia and intrauterine growth restriction. Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide synthetized in trophoblasts at the maternal-placental interface. It regulates the function of trophoblast cells and their interaction with decidual leukocytes. By means of a murine model of pregnancy in normal maternal background with VIP-deficient trophoblast cells, here we demonstrate that trophoblast VIP is critical for trophoblast function: VIP gene haploinsufficiency results in lower matrix metalloproteinase 9 expression, and reduced migration and invasion capacities. A reduced number of regulatory T cells at the implantation sites along with a lower expression of proangiogenic and antiinflammatory markers were also observed. Findings detected in the implantation sites at early stages were followed by an abnormal placental structure and lower fetal weight. This effect was overcome by VIP treatment of the early pregnant mice. Our results support the relevance of trophoblast-synthesized VIP as a critical factor in vivo for trophoblast-cell function and immune homeostasis maintenance in mouse pregnancy. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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31. Control of the inflammatory response during pregnancy: potential role of VIP as a regulatory peptide.
- Author
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Ramhorst, Rosanna, Calo, Guillermina, Paparini, Daniel, Vota, Daiana, Hauk, Vanesa, Gallino, Lucila, Merech, Fatima, Grasso, Esteban, and Leirós, Claudia Pérez
- Subjects
INFLAMMATION ,PREGNANCY ,VASOACTIVE intestinal peptide ,CELL communication ,MACROPHAGES - Abstract
A network of cell–cell communications through contact and soluble factors supports the maternal–placental interaction and provides a suitable environment for fetal growth. Trophoblast cells take center stage at these loops: they interact with maternal leukocytes to sustain the varying demands of gestation, and they synthesize hormones, cytokines among other factors that contribute to the maintenance of immune homeostasis. Here, we discuss vasoactive intestinal peptide (VIP) and its potential as a regulatory neuropeptide in pregnancy. VIP is synthesized by trophoblast cells; it regulates trophoblast cell function and interaction with the major immune cell populations present in the pregnant uterus. VIP activity produces an anti‐inflammatory microenvironment by modulating the functional profile of monocytes, macrophages, and regulatory T cells. Trophoblast VIP inhibits neutrophil extracellular trap formation and accelerates neutrophil apoptosis, enabling their silent clearance by phagocytic cells. The effects of VIP on the trophoblast–immune interaction are consistent with its regulatory role throughout pregnancy for immune homeostasis maintenance. These observations may provide new clues for pharmacological targeting of pregnancy complications associated with exacerbated inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
32. Impairment of first-trimester trophoblast cell function by ZIKV infection. Role of VIP in the trophoblast response to the virus.
- Author
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Vota, Daiana, Paparini, Daniel, Torti, Florencia, Merech, Fátima, Hauk, Vanesa, Giovannoni, Federico, Calo, Guillermina, Ramhorst, Rosanna, Garcia, Cybele, and Leirós, Claudia Pérez
- Published
- 2019
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33. LPS FROM PORPHYROMONAS GINGIVALIS IMPAIRS TROPHOBLAST CELL FUNCTION AND IMMUNE-TROPHOBLAST INTERACTION
- Author
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Hauk, Vanesa, Calo, Guillermina, Muñoz, María Román, Vota, Daiana, Merech, Fátima, Paparini, Daniel, Ramhorst, Rosanna, and Leirós, Claudia Pérez
- Published
- 2019
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34. Homeostasis loss in VIP deficient mice is associated with altered regulatory T cells recruitment
- Author
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Gallino, Lucila, Hauk, Vanesa, Grasso, Esteban, Palligas, Marcos, Saraco, Nora, Berensztein, Esperanza, Pascuali, Natalia, Parborell, Fernanda, Waschek, James, Leirós, Claudia Perez, and Ramhorst, Rosanna
- Published
- 2019
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35. Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR pathways in human trophoblast cells
- Author
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Merech, Fatima, Soczewski, Elizabeth, Hauk, Vanesa, Paparini, Daniel, Ramhorst, Rosanna, Leirós, Claudia Pérez, and Vota, Daiana
- Published
- 2019
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- View/download PDF
36. VIP in vivo treatment modulates maternal macrophage activation profile and efferocytic ability in the CBAxDBA resorption prone model
- Author
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Gallino Lucila, Calo Guillermina, Hauk Vanesa, Fraccaroli Laura, Grasso Esteban, Vermeulen Monica, Perez Leiros Claudia, and Ramhorst Rosanna
- Subjects
Immunology ,Immunology and Allergy - Published
- 2015
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37. Galectin-1 (Gal1) and N-glycans regulate the spontaneous development of sialadenitis
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Martínez Allo Verónica, Hauk Vanesa, Morales Rosa, Stupirski Juan, Pinto Nicolas, Perez Leiros Claudia, Rabinovich Gabriel, and Toscano Marta
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Immunology ,Immunology and Allergy - Published
- 2015
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38. Role of vip in trophoblast invasion, vascular remodeling and immunomodulation during early pregnancy
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Paparini, Daniel, Choudhury, Ruhul, Fin-Sell, Sarah, Karolczack-Bayatti, Magda, Vota, Daiana, Hauk, Vanesa, Ramhorst, Rosanna, Aplin, John, and Leiros, Claudia Perez
- Published
- 2017
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- View/download PDF
39. VIP modulates glucose uptake by trophoblast cells and is involved in murine fetal growth
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Vota, Daiana, Merech, Fátima, Hauk, Vanesa, Paparini, Daniel, Calo, Guillermina, Gallino, Lucila, Ramhorst, Rosanna, Waschek, James, and Leirós, Claudia Pérez
- Published
- 2017
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- View/download PDF
40. Relevance of endogenous VIP at the early maternal-placental interface: Functional profile of trophoblast giant cells from normal and VIP-deficient mice
- Author
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Hauk, Vanesa, Grasso, Esteban, Gallino, Lucila, Calo, Guillermina, Ramhorst, Rosanna, Waschek, James, and Leiros, Claudia Perez
- Published
- 2015
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- View/download PDF
41. Decoding the chemokine network that links leukocytes with decidual cells and the trophoblast during early implantation.
- Author
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Ramhorst, Rosanna, Grasso, Esteban, Paparini, Daniel, Hauk, Vanesa, Gallino, Lucila, Calo, Guillermina, Vota, Daiana, and Pérez Leirós, Claudia
- Published
- 2016
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- View/download PDF
42. Differential Migration and Activation Profile of Monocytes after Trophoblast Interaction.
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Grasso, Esteban, Paparini, Daniel, Hauk, Vanesa, Salamone, Gabriela, Leiros, Claudia Perez, and Ramhorst, Rosanna
- Subjects
MONOCYTES ,TROPHOBLAST ,CELL communication ,WOUND healing ,CD14 antigen ,MACROPHAGES ,APOPTOSIS - Abstract
Macrophages at the maternal-placental interface coordinate opposite demands under the control of trophoblast cells such as the response against pathogens on one hand, and apoptotic cell clearance and wound healing with the production of suppressor cytokines. Here, we investigated whether trophoblast cells induce maternal monocyte activation towards an alternative activated macrophage profile and whether bacterial or viral stimuli modulate their migratory properties. We used an in vitro model of the maternal-placental interface represented by co-cultures of CD14+ cells isolated from fertile women with first trimester trophoblast cell line (Swan-71 cells) in the presence or absence of pathogen associated molecular pattern (PAMP) stimuli lipopolysaccharide (LPS), peptidoglycan (PGN) or poly [I:C]). Maternal CD14+ cells showed increased CD16 and CD39 expression, both markers associated to an alternative activation profile, with no changes in CD80 expression after trophoblast cell interaction. These changes were accompanied by increased IL-10 and decreased IL-12 production by CD14+ cells. After stimulation with LPS, PGN or poly [I:C], monocytes co-cultured with trophoblast cells had lower production of TNF-α and IL-1β compared with non co-cultured monocytes. Interestingly, monocyte migration towards trophoblast cells was prevented in the presence of LPS or PGN but not after 24h of stimulation with poly [I:C]. LPS or PGN also decreased CCR5, CXCL-8 and CCL5 expression. Finally, trophoblast cells co-cultured with monocytes in the presence of pathological stimuli failed to increase chemokine expression, indicating a bidirectional effect. In conclusion, trophoblast might ‘instruct’ maternal monocytes to express an alternative activation profile and restrain their early recruitment under pathological threats as one of the first strategies to avoid potential tissue damage at the maternal-placental interface. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
43. Contribution of Vasoactive Intestinal Peptide to Immune Homeostasis in Trophoblast-Maternal Leukocyte Interaction under LPS Stimulation.
- Author
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Fraccaroli, Laura, Grasso, Esteban, Hauk, Vanesa, Cortelezzi, Marta, Pérez Leirós, Claudia, and Ramhorst, Rosanna
- Abstract
Background/Aims: The maternal-fetal interface is a unique immunological site that generates an adequate microenvironment during pregnancy, recognizing and eliminating infections and tolerating the trophoblast/placenta unit. For that purpose, trophoblast cells display several tolerogenic mechanisms to allow fetal survival, such as production of the neuropeptide vasoactive intestinal peptide (VIP). Here we investigated the contribution of VIP to maintain homeostasis at the maternal-placental interface under lipopolysaccharide (LPS) stimulation. Methods: We performed cocultures between trophoblast cells (Swan-71 cell line) and maternal leukocytes obtained from fertile women as an in vitro model of maternal-placental interaction, and we focused on the effects of LPS on the modulation of VIP and their receptors (VPAC
1 and VPAC2 ). Results: VIP could prevent the upregulation of IL-6, MCP-1, and nitrite production and maintain the production of IL-10 and TGF-β under LPS (10 µg/ml) stimulation after 48 h of coculture. To gain deeper insight into the mechanisms of how VIP could contribute to a tolerogenic microenvironment even in the presence of LPS, we investigated VIP production by maternal leukocytes and observed a significant increase in the frequency of CD4+VIP+ cells after interaction with Swan-71 cells in the presence of LPS. LPS increased VIP and inducible receptor VPAC2 expression directly on trophoblast cells in a dose- and time-dependent manner. Conclusions: The present results suggest that VIP might act as an additional homeostatic mechanism during early stages at the maternal-placental interface to control exacerbated inflammatory responses such as the ones observed in intrauterine infections. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]- Published
- 2013
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44. Pregnancy Entails a Metabolic Rewiring of Maternal Circulating Neutrophils.
- Author
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Calo, Guillermina, Merech, Fátima, Sabbione, Florencia, Hauk, Vanesa, Lara, Brenda, Doga, Luciana, D'eramo, Luciana, Squassi, Aldo, Ramhorst, Rosanna, Trevani, Analía, Vota, Daiana, and Leirós, Claudia Pérez
- Subjects
- *
CELL physiology , *FATTY acid oxidation , *CELL morphology , *METABOLIC regulation , *CELL populations , *TROPHOBLAST , *NEUTROPHILS - Abstract
ABSTRACT Immunometabolism is an emerging growing field that focuses on the role of cellular metabolism in the regulation of immune cell function and fate. Thus, proliferation, differentiation, activation, and function of immune cell populations are modulated by reprogramming their fueling and metabolic pathways. Pregnancy entails a fine immune and metabolic regulation of the maternal−fetal interaction to assist the energetic demands of the fetus where trophoblast cells have a central role. Maternal neutrophil functional shaping by trophoblast cells has been proposed though their metabolic conditioning during pregnancy has not been studied yet. Here, we explored the effects of trophoblast‐derived factors on the metabolic rewiring of neutrophils from nonpregnant women and its impact on central functions like reactive oxygen species (ROS) production, neutrophil extracellular trap (NET) release, and migration. In parallel, the immunometabolic status and function of neutrophils isolated from pregnant women (16−20 weeks) was compared with nonpregnant age‐matched control samples. Trophoblast‐derived factors induced glucose uptake and lipid droplet accumulation without activating ROS production or NET release. Conditioned media from trophoblast cells also inhibited PMA‐induced NETosis partly by impairing glucose uptake in neutrophils. In turn, neutrophils from pregnant women had increased basal ROS production, lipid accumulation, and glucose uptake compared to neutrophils from nonpregnant women, accompanied by a higher release of PMA‐induced NETs. Interestingly, PMA‐induced NETs was blocked by a fatty acid oxidation inhibitor in neutrophils from pregnant women indicating the contribution of fatty acid metabolism to neutrophil activity during pregnancy. Results are consistent with immunometabolic mechanisms underlying the functional shaping of neutrophils during pregnancy and point out the contribution of trophoblast‐derived factors to their metabolic profiling. These findings provide novel immunometabolic clues to understand immune homeostasis maintenance during pregnancy and raise the clinical potential of monitoring neutrophil metabolism during normal and complicated pregnancies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells.
- Author
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Merech, Fatima, Soczewski, Elizabeth, Hauk, Vanesa, Paparini, Daniel, Ramhorst, Rosanna, Vota, Daiana, and Pérez Leirós, Claudia
- Subjects
VASOACTIVE intestinal peptide ,GLUCOSE ,AMINO acids ,MTOR protein ,GENE expression - Abstract
The transport of nutrients across the placenta involves trophoblast cell specific transporters modulated through the mammalian target of rapamycin (mTOR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast cell migration and invasion. Here we explored the effect of VIP on glucose and System A amino acid uptake by human trophoblast-derived cells (Swan 71 and BeWo cell lines). VIP activated D-glucose specific uptake in single cytotrophoblast cells in a concentration-dependent manner through PKA, MAPK, PI3K and mTOR signalling pathways. Glucose uptake was reduced in VIP-knocked down cytotrophoblast cells. Also, VIP stimulated System A amino acid uptake and the expression of GLUT1 glucose transporter and SNAT1 neutral amino acid transporter. VIP increased mTOR expression and mTOR/S6 phosphorylation whereas VIP silencing reduced mTOR mRNA and protein expression. Inhibition of mTOR signalling with rapamycin reduced the expression of endogenous VIP and of VIP-induced S6 phosphorylation. Our findings support a role of VIP in the transport of glucose and neutral amino acids in cytotrophoblast cells through mTOR-regulated pathways and they are instrumental for understanding the physiological regulation of nutrient sensing by endogenous VIP at the maternal-foetal interface. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
46. Vasoactive Intestinal Peptide modulates trophoblast-derived cell line function and interaction with phagocytic cells through autocrine pathways.
- Author
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Vota, Daiana, Paparini, Daniel, Hauk, Vanesa, Toro, Ayelén, Merech, Fatima, Varone, Cecilia, Ramhorst, Rosanna, and Pérez Leirós, Claudia
- Published
- 2016
- Full Text
- View/download PDF
47. VIP treatment prevents embryo resorption by modulating efferocytosis and activation profile of maternal macrophages in the CBAxDBA resorption prone model.
- Author
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Gallino, Lucila, Calo, Guillermina, Hauk, Vanesa, Fraccaroli, Laura, Grasso, Esteban, Vermeulen, Mónica, Leirós, Claudia Pérez, and Ramhorst, Rosanna
- Published
- 2016
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- View/download PDF
48. Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua.
- Author
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Alippe Y, Wang L, Coskun R, Muraro SP, Zhao FR, Elam-Noll M, White JM, Vota DM, Hauk VC, Gordon JI, Handley SA, and Diamond MS
- Subjects
- Female, Animals, Pregnancy, Mice, Mice, Inbred C57BL, Mice, Knockout, Immunity, Innate, Pregnancy Complications, Infectious immunology, Pregnancy Complications, Infectious virology, Disease Models, Animal, Interferon Type I metabolism, Interferon Type I immunology, Signal Transduction immunology, Adaptor Proteins, Signal Transducing metabolism, Adaptor Proteins, Signal Transducing genetics, Placenta immunology, Placenta virology, Placenta metabolism, Zika Virus Infection immunology, Zika Virus Infection virology, Zika Virus immunology, Zika Virus physiology, Decidua immunology, Decidua virology, Decidua metabolism, Fetus immunology, Fetus virology, Trophoblasts immunology, Trophoblasts virology, Trophoblasts metabolism, Receptor, Interferon alpha-beta genetics, Receptor, Interferon alpha-beta metabolism
- Abstract
The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1-/- or Mavs-/- placentas was associated with greater infection of the adjacent immunocompetent decidua, and heterozygous Mavs+/- or Ifnar1+/- dams carrying immunodeficient fetuses sustained greater maternal viremia and tissue infection than dams carrying wild-type fetuses. Thus, MAVS-IFN signaling in the fetus restricts ZIKV infection in junctional zone trophoblasts, which modulates dissemination and outcome for both the fetus and the pregnant mother., (© 2024 Alippe et al.)
- Published
- 2024
- Full Text
- View/download PDF
49. Trophoblast cells primed with vasoactive intestinal peptide enhance monocyte migration and apoptotic cell clearance through αvβ3 integrin portal formation in a model of maternal-placental interaction.
- Author
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Paparini D, Grasso E, Calo G, Vota D, Hauk V, Ramhorst R, and Leirós CP
- Subjects
- Apoptosis drug effects, Female, Humans, Monocytes metabolism, Placenta drug effects, Placenta metabolism, Pregnancy, Trophoblasts drug effects, Vasoactive Intestinal Peptide pharmacology, Integrin alphaVbeta3 metabolism, Trophoblasts metabolism
- Abstract
Study Hypothesis: Is apoptotic cell phagocytosis by monocytes modulated by pathways elicited by vasoactive intestinal peptide (VIP) action on trophoblast?, Study Finding: Targeting trophoblast cells with VIP induces monocyte migration, polarization to anti-inflammatory phenotypes and apoptotic trophoblast cell clearance which involves increased αvβ3 integrin expression on phagocytic cells and binding to thrombospondin 1., What Is Known Already: Monocytes recruited to the maternal-placental interface interact with trophoblast cells and differentiate to alternatively activated macrophages involved in the silent clearance of apoptotic cells. Vasoactive intestinal peptide (VIP) is an immunomodulatory polypeptide synthesized at the human placenta that can target both trophoblast cells and monocytes/macrophages. Integrin αvβ3 and thrombospondin 1 are involved in the formation of a phagocytic portal for the immunosuppressant clearance of apoptotic cells., Study Design, Samples/materials, Methods: This is a laboratory-based study studying monocytes isolated from peripheral blood of healthy women (n = 33) and their interaction in vitro with first trimester trophoblast cell lines. Peripheral blood monocytes were isolated from healthy volunteers by Percoll gradient and tested in co-culture settings with first trimester trophoblast cell lines (Swan 71 and HTR8) or with trophoblast cell conditioned media obtained in the presence or absence of 10 or 100 nM VIP. The effect of VIP-conditioned media on monocyte migration was assessed through transwell systems and monocyte/macrophage phenotype was determined by flow cytometry. Phagocytosis of apoptotic cells and the mechanisms involved in phagocytic portal formation were assessed by flow cytometry, confocal microscopy, immunological blockade and RT-PCR., Main Results and the Role of Chance: Exposing cells to 100 nM VIP increased the migration of monocytes toward trophoblast cell conditioned media (VIP conditioned medium) (P < 0.05 versus conditioned media from cells not exposed to VIP) and contributed to the monocytes acquiring an anti-inflammatory profile with increased CD39 and IL-10 expression (P < 0.05). Phagocytosis of apoptotic trophoblast cells by monocytes and monocyte-differentiated macrophages was increased by VIP conditioned medium (P < 0.05 versus media conditioned in the absence of VIP or direct addition of 100 nM VIP). The boosting effect of VIP conditioned medium on phagocytosis involved increased expression and re-localization of αvβ3 integrin on phagocytic cells along with enhanced expression of thrombospondin 1 on trophoblast cells., Limitations, Reasons for Caution: The conclusions are based on in vitro experiments with monocytes drawn from peripheral blood of healthy individuals and trophoblast cell lines and we were unable to ascertain that these mechanisms operate similarly in vivo. We cannot rule out a differential behavior of either trophoblast cells targeted in vivo with VIP, or primary cultures of first trimester trophoblast cells assayed in vitro., Wider Implications of the Findings: The results presented provide new clues for immune and trophoblast cell pharmacological targeting in pregnancy complications of immunopathologic nature., Study Funding/competing Interests: This work was funded by the National Agency of Sciences and Technology ANPCyT (PICT 2011-0144), National Research Council CONICET (PIP 602/2012) and University of Buenos Aires (UBACyT 20020130100040BA) to C.P.L. The authors have no conflicts of interest to disclose., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
- View/download PDF
50. VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast-maternal leukocyte interaction.
- Author
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Fraccaroli L, Grasso E, Hauk V, Paparini D, Soczewski E, Mor G, Pérez Leirós C, and Ramhorst R
- Subjects
- Cell Line, Coculture Techniques, Female, Humans, In Vitro Techniques, Interleukin-10 biosynthesis, Leukocytes cytology, Pregnancy, Pregnancy Trimester, First, Real-Time Polymerase Chain Reaction, T-Lymphocytes, Regulatory cytology, T-Lymphocytes, Regulatory immunology, Transforming Growth Factor beta1 biosynthesis, Transforming Growth Factor beta1 metabolism, Trophoblasts cytology, Cell Communication, Leukocytes drug effects, T-Lymphocytes, Regulatory drug effects, Trophoblasts drug effects, Vasoactive Intestinal Peptide pharmacology
- Abstract
Inducible regulatory T cells (Tregs) exert a timely and efficient immunosuppressive action at the critical peri-implantation stage essential for maternal tolerance to the conceptus. Vasoactive intestinal peptide (VIP) promotes anti-inflammatory and tolerogenic profiles through binding to VIP receptors on immune cells. We evaluated whether VIP produced by trophoblast cells induces Tregs during the early interaction of maternal leukocytes with trophoblast cells, thus contributing to maternal tolerance. We used an in vitro model of maternal leukocyte-trophoblast cell interaction represented by cocultures of fertile women's PBMCs with a human trophoblast cell line (Swan-71) and evaluated the effect of VIP added exogenously and of the endogenous polypeptide. VIP increased the frequency of CD4(+)CD25(+)FoxP3(+) cells after coculture, and these cells were able to suppress the maternal alloresponse. VIP also increased the frequency of CD4(+)IL10(+) and CD4(+)TGFβ(+) cells, but it did not modulate IFN-γ or IL-17 production. Swan-71 secreted VIP, and their coculture with maternal PBMCs significantly increased the frequency of Tregs. This effect was even more pronounced if the trophoblast cells had been pretreated with VIP. In both situations, the VIP antagonist prevented the increase in the frequency of CD4(+)Foxp3(+) cells, reflecting a specific effect of the polypeptide after the interaction with Swan-71 cells. Finally, the increase in CD4(+)CD25(+)FoxP3(+) frequency was prevented by an anti-TGF-β Ab and a VIP antagonist. These results suggest that VIP could have an active role in the immunoregulatory processes operating in the maternal-placental interface by contributing to the induction of Tregs through a mechanism involving TGF-β1., (© Society for Leukocyte Biology.)
- Published
- 2015
- Full Text
- View/download PDF
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