Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response

Autores
Fraccaroli, Laura Virginia; Grasso, Esteban Nicolas; Hauk, Vanesa Cintia; Cortelezzi, M.; Calo, Guillermina; Perez Leiros, Claudia; Ramhorst, Rosanna Elizabeth
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Successful embryo implantation occurs followed by a local inflammatory/Th1 response, subsequently redirected towards a tolerogenic predominant profile. The lack of a control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as recurrent spontaneous abortions (RSA). Considering that VIP mediates anti-inflammatory and tolerogenic effects in several conditions we hypothesized that VIP may contribute to the tolerance towards trophoblast antigens during the early interaction of maternal leukocytes and trophoblast cells. Here we investigated VIP/VPAC system activity and expression on maternal PBMCs after the interaction with immortalized trophoblast cells (Swan-71 cell line) as an in vitro model of feto-maternal interaction and we analyzed whether it modulates maternal Treg/Th1 responses. We also investigated the contribution of endogenous VIP/VPAC system to RSA pathogenesis. VIP significantly decreased T-bet expression, reduced MCP-1 and nitrite production in co-cultures of fertile women PBMCs with trophoblast cells; while it increased the frequency of CD4+CD25+Foxp3+ cells, TFG expression and IL-10 secretion. These effects were prevented by VIP specific antagonist. Interestingly, PBMCs from RSA patients displayed significantly higher T-bet expression, lower Treg frequency and lower frequency of VIP-producer CD4 lymphocytes after the interaction with trophoblast cells. Moreover, the patients displayed significantly lower frequency of endometrial CD4+VIP+ cells in comparison with fertile women. Conclusion: VIP showed a Th1-limiting and Treg-promoting response in vitro that would favor early pregnancy outcome. Since RSA patients displayed defects in the VIP/VPAC system, this neuropeptide could arise as a promising candidate for diagnostic biomarker or surrogate biomarker for recurrent spontaneous abortions.
Fil: Fraccaroli, Laura Virginia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Grasso, Esteban Nicolas. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Hauk, Vanesa Cintia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Cortelezzi, M.. Sociedad Argentina de Endocrinología Ginecológica y Reproductiva; Argentina
Fil: Calo, Guillermina. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Perez Leiros, Claudia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; 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: Ramhorst, Rosanna Elizabeth. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Materia
VIP
Materno-tolerance
recurrent spontaneous abortions
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/275114
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic responseFraccaroli, Laura VirginiaGrasso, Esteban NicolasHauk, Vanesa CintiaCortelezzi, M.Calo, GuillerminaPerez Leiros, ClaudiaRamhorst, Rosanna ElizabethVIPMaterno-tolerancerecurrent spontaneous abortionshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Successful embryo implantation occurs followed by a local inflammatory/Th1 response, subsequently redirected towards a tolerogenic predominant profile. The lack of a control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as recurrent spontaneous abortions (RSA). Considering that VIP mediates anti-inflammatory and tolerogenic effects in several conditions we hypothesized that VIP may contribute to the tolerance towards trophoblast antigens during the early interaction of maternal leukocytes and trophoblast cells. Here we investigated VIP/VPAC system activity and expression on maternal PBMCs after the interaction with immortalized trophoblast cells (Swan-71 cell line) as an in vitro model of feto-maternal interaction and we analyzed whether it modulates maternal Treg/Th1 responses. We also investigated the contribution of endogenous VIP/VPAC system to RSA pathogenesis. VIP significantly decreased T-bet expression, reduced MCP-1 and nitrite production in co-cultures of fertile women PBMCs with trophoblast cells; while it increased the frequency of CD4+CD25+Foxp3+ cells, TFG expression and IL-10 secretion. These effects were prevented by VIP specific antagonist. Interestingly, PBMCs from RSA patients displayed significantly higher T-bet expression, lower Treg frequency and lower frequency of VIP-producer CD4 lymphocytes after the interaction with trophoblast cells. Moreover, the patients displayed significantly lower frequency of endometrial CD4+VIP+ cells in comparison with fertile women. Conclusion: VIP showed a Th1-limiting and Treg-promoting response in vitro that would favor early pregnancy outcome. Since RSA patients displayed defects in the VIP/VPAC system, this neuropeptide could arise as a promising candidate for diagnostic biomarker or surrogate biomarker for recurrent spontaneous abortions.Fil: Fraccaroli, Laura Virginia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Grasso, Esteban Nicolas. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Hauk, Vanesa Cintia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Cortelezzi, M.. Sociedad Argentina de Endocrinología Ginecológica y Reproductiva; ArgentinaFil: Calo, Guillermina. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Perez Leiros, Claudia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; 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; ArgentinaFil: Ramhorst, Rosanna Elizabeth. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaWiley Blackwell Publishing, Inc2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/275114Fraccaroli, Laura Virginia; Grasso, Esteban Nicolas; Hauk, Vanesa Cintia; Cortelezzi, M.; Calo, Guillermina; et al.; Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 170; 3; 12-2012; 310-3200009-9104CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/cei/article-abstract/170/3/310/6428978info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2249.2012.04668.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-03T08:42:59Zoai:ri.conicet.gov.ar:11336/275114instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-03 08:43:00.121CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
title Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
spellingShingle Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
Fraccaroli, Laura Virginia
VIP
Materno-tolerance
recurrent spontaneous abortions
title_short Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
title_full Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
title_fullStr Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
title_full_unstemmed Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
title_sort Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response
dc.creator.none.fl_str_mv Fraccaroli, Laura Virginia
Grasso, Esteban Nicolas
Hauk, Vanesa Cintia
Cortelezzi, M.
Calo, Guillermina
Perez Leiros, Claudia
Ramhorst, Rosanna Elizabeth
author Fraccaroli, Laura Virginia
author_facet Fraccaroli, Laura Virginia
Grasso, Esteban Nicolas
Hauk, Vanesa Cintia
Cortelezzi, M.
Calo, Guillermina
Perez Leiros, Claudia
Ramhorst, Rosanna Elizabeth
author_role author
author2 Grasso, Esteban Nicolas
Hauk, Vanesa Cintia
Cortelezzi, M.
Calo, Guillermina
Perez Leiros, Claudia
Ramhorst, Rosanna Elizabeth
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv VIP
Materno-tolerance
recurrent spontaneous abortions
topic VIP
Materno-tolerance
recurrent spontaneous abortions
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Successful embryo implantation occurs followed by a local inflammatory/Th1 response, subsequently redirected towards a tolerogenic predominant profile. The lack of a control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as recurrent spontaneous abortions (RSA). Considering that VIP mediates anti-inflammatory and tolerogenic effects in several conditions we hypothesized that VIP may contribute to the tolerance towards trophoblast antigens during the early interaction of maternal leukocytes and trophoblast cells. Here we investigated VIP/VPAC system activity and expression on maternal PBMCs after the interaction with immortalized trophoblast cells (Swan-71 cell line) as an in vitro model of feto-maternal interaction and we analyzed whether it modulates maternal Treg/Th1 responses. We also investigated the contribution of endogenous VIP/VPAC system to RSA pathogenesis. VIP significantly decreased T-bet expression, reduced MCP-1 and nitrite production in co-cultures of fertile women PBMCs with trophoblast cells; while it increased the frequency of CD4+CD25+Foxp3+ cells, TFG expression and IL-10 secretion. These effects were prevented by VIP specific antagonist. Interestingly, PBMCs from RSA patients displayed significantly higher T-bet expression, lower Treg frequency and lower frequency of VIP-producer CD4 lymphocytes after the interaction with trophoblast cells. Moreover, the patients displayed significantly lower frequency of endometrial CD4+VIP+ cells in comparison with fertile women. Conclusion: VIP showed a Th1-limiting and Treg-promoting response in vitro that would favor early pregnancy outcome. Since RSA patients displayed defects in the VIP/VPAC system, this neuropeptide could arise as a promising candidate for diagnostic biomarker or surrogate biomarker for recurrent spontaneous abortions.
Fil: Fraccaroli, Laura Virginia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Grasso, Esteban Nicolas. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Hauk, Vanesa Cintia. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Cortelezzi, M.. Sociedad Argentina de Endocrinología Ginecológica y Reproductiva; Argentina
Fil: Calo, Guillermina. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Perez Leiros, Claudia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; 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: Ramhorst, Rosanna Elizabeth. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
description Successful embryo implantation occurs followed by a local inflammatory/Th1 response, subsequently redirected towards a tolerogenic predominant profile. The lack of a control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as recurrent spontaneous abortions (RSA). Considering that VIP mediates anti-inflammatory and tolerogenic effects in several conditions we hypothesized that VIP may contribute to the tolerance towards trophoblast antigens during the early interaction of maternal leukocytes and trophoblast cells. Here we investigated VIP/VPAC system activity and expression on maternal PBMCs after the interaction with immortalized trophoblast cells (Swan-71 cell line) as an in vitro model of feto-maternal interaction and we analyzed whether it modulates maternal Treg/Th1 responses. We also investigated the contribution of endogenous VIP/VPAC system to RSA pathogenesis. VIP significantly decreased T-bet expression, reduced MCP-1 and nitrite production in co-cultures of fertile women PBMCs with trophoblast cells; while it increased the frequency of CD4+CD25+Foxp3+ cells, TFG expression and IL-10 secretion. These effects were prevented by VIP specific antagonist. Interestingly, PBMCs from RSA patients displayed significantly higher T-bet expression, lower Treg frequency and lower frequency of VIP-producer CD4 lymphocytes after the interaction with trophoblast cells. Moreover, the patients displayed significantly lower frequency of endometrial CD4+VIP+ cells in comparison with fertile women. Conclusion: VIP showed a Th1-limiting and Treg-promoting response in vitro that would favor early pregnancy outcome. Since RSA patients displayed defects in the VIP/VPAC system, this neuropeptide could arise as a promising candidate for diagnostic biomarker or surrogate biomarker for recurrent spontaneous abortions.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/275114
Fraccaroli, Laura Virginia; Grasso, Esteban Nicolas; Hauk, Vanesa Cintia; Cortelezzi, M.; Calo, Guillermina; et al.; Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 170; 3; 12-2012; 310-320
0009-9104
CONICET Digital
CONICET
url http://hdl.handle.net/11336/275114
identifier_str_mv Fraccaroli, Laura Virginia; Grasso, Esteban Nicolas; Hauk, Vanesa Cintia; Cortelezzi, M.; Calo, Guillermina; et al.; Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental–maternal leucocyte interaction impair the maternal tolerogenic response; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 170; 3; 12-2012; 310-320
0009-9104
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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