Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental-maternal leucocyte interaction impair the maternal tolerogenic response
Successful embryo implantation occurs followed by a local inflammatory/T helper type 1 (Th1) response, subsequently redirected towards a tolerogenic predominant profile. The lack of control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as rec...
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todo:paper_00099104_v170_n3_p310_Fraccaroli2023-10-03T14:08:49Z Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental-maternal leucocyte interaction impair the maternal tolerogenic response Fraccaroli, L. Grasso, E. Hauk, V. Cortelezzi, M. Calo, G. Pérez Leirós, C. Ramhorst, R. Maternal tolerance Recurrent spontaneous abortions VIP forkhead transcription factor interleukin 10 transforming growth factor beta vasoactive intestinal polypeptide adult article CD4+ T lymphocyte clinical article female human in vitro study leukocyte peripheral blood mononuclear cell placenta priority journal protein expression spontaneous abortion trophoblast Adult Cell Communication Embryo Implantation Embryo Loss Endometrium Female Humans Immune Tolerance Inflammation Mediators Leukocytes Leukocytes, Mononuclear Placenta Pregnancy Receptors, Vasoactive Intestinal Peptide T-Box Domain Proteins T-Lymphocytes, Regulatory Trophoblasts Vasoactive Intestinal Peptide Successful embryo implantation occurs followed by a local inflammatory/T helper type 1 (Th1) response, subsequently redirected towards a tolerogenic predominant profile. The lack of control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as recurrent spontaneous abortions (RSA). Considering that vasoactive intestinal peptide (VIP) mediates anti-inflammatory and tolerogenic effects in several conditions we hypothesized that VIP might contribute to tolerance towards trophoblast antigens during the early interaction of maternal leucocytes and trophoblast cells. In this study we investigated VIP/VPAC system activity and expression on maternal peripheral blood mononuclear cells (PBMCs) after interaction with immortalized trophoblast cells (Swan-71 cell line) as an in-vitro model of feto-maternal interaction, and we analysed whether it modulates maternal regulatory T cell (Treg)/Th1 responses. We also investigated the contribution of the endogenous VIP/VPAC system to RSA pathogenesis. VIP decreased T-bet expression significantly, reduced monocyte chemotactic protein-1 (MCP-1) and nitrite production in co-cultures of PBMCs from fertile women with trophoblast cells; while it increased the frequency of CD4+CD25+ forkhead box protein 3 (Foxp3)+ cells, transforming growth factor (TGF)-β expression and interleukin (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 a significantly lower frequency of endometrial CD4+VIP+ cells in comparison with fertile women. VIP showed a Th1-limiting and Treg-promoting response in vitro that would favour early pregnancy outcome. Because RSA patients displayed defects in the VIP/VPAC system, this neuropeptide could be a promising candidate for diagnostic biomarker or surrogate biomarker for recurrent spontaneous abortions. © 2012 British Society for Immunology. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00099104_v170_n3_p310_Fraccaroli |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Maternal tolerance Recurrent spontaneous abortions VIP forkhead transcription factor interleukin 10 transforming growth factor beta vasoactive intestinal polypeptide adult article CD4+ T lymphocyte clinical article female human in vitro study leukocyte peripheral blood mononuclear cell placenta priority journal protein expression spontaneous abortion trophoblast Adult Cell Communication Embryo Implantation Embryo Loss Endometrium Female Humans Immune Tolerance Inflammation Mediators Leukocytes Leukocytes, Mononuclear Placenta Pregnancy Receptors, Vasoactive Intestinal Peptide T-Box Domain Proteins T-Lymphocytes, Regulatory Trophoblasts Vasoactive Intestinal Peptide |
| spellingShingle |
Maternal tolerance Recurrent spontaneous abortions VIP forkhead transcription factor interleukin 10 transforming growth factor beta vasoactive intestinal polypeptide adult article CD4+ T lymphocyte clinical article female human in vitro study leukocyte peripheral blood mononuclear cell placenta priority journal protein expression spontaneous abortion trophoblast Adult Cell Communication Embryo Implantation Embryo Loss Endometrium Female Humans Immune Tolerance Inflammation Mediators Leukocytes Leukocytes, Mononuclear Placenta Pregnancy Receptors, Vasoactive Intestinal Peptide T-Box Domain Proteins T-Lymphocytes, Regulatory Trophoblasts Vasoactive Intestinal Peptide Fraccaroli, L. Grasso, E. Hauk, V. Cortelezzi, M. Calo, G. Pérez Leirós, C. Ramhorst, R. Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental-maternal leucocyte interaction impair the maternal tolerogenic response |
| topic_facet |
Maternal tolerance Recurrent spontaneous abortions VIP forkhead transcription factor interleukin 10 transforming growth factor beta vasoactive intestinal polypeptide adult article CD4+ T lymphocyte clinical article female human in vitro study leukocyte peripheral blood mononuclear cell placenta priority journal protein expression spontaneous abortion trophoblast Adult Cell Communication Embryo Implantation Embryo Loss Endometrium Female Humans Immune Tolerance Inflammation Mediators Leukocytes Leukocytes, Mononuclear Placenta Pregnancy Receptors, Vasoactive Intestinal Peptide T-Box Domain Proteins T-Lymphocytes, Regulatory Trophoblasts Vasoactive Intestinal Peptide |
| description |
Successful embryo implantation occurs followed by a local inflammatory/T helper type 1 (Th1) response, subsequently redirected towards a tolerogenic predominant profile. The lack of control of this initial local inflammatory response may be an underlying cause of early pregnancy complications as recurrent spontaneous abortions (RSA). Considering that vasoactive intestinal peptide (VIP) mediates anti-inflammatory and tolerogenic effects in several conditions we hypothesized that VIP might contribute to tolerance towards trophoblast antigens during the early interaction of maternal leucocytes and trophoblast cells. In this study we investigated VIP/VPAC system activity and expression on maternal peripheral blood mononuclear cells (PBMCs) after interaction with immortalized trophoblast cells (Swan-71 cell line) as an in-vitro model of feto-maternal interaction, and we analysed whether it modulates maternal regulatory T cell (Treg)/Th1 responses. We also investigated the contribution of the endogenous VIP/VPAC system to RSA pathogenesis. VIP decreased T-bet expression significantly, reduced monocyte chemotactic protein-1 (MCP-1) and nitrite production in co-cultures of PBMCs from fertile women with trophoblast cells; while it increased the frequency of CD4+CD25+ forkhead box protein 3 (Foxp3)+ cells, transforming growth factor (TGF)-β expression and interleukin (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 a significantly lower frequency of endometrial CD4+VIP+ cells in comparison with fertile women. VIP showed a Th1-limiting and Treg-promoting response in vitro that would favour early pregnancy outcome. Because RSA patients displayed defects in the VIP/VPAC system, this neuropeptide could be a promising candidate for diagnostic biomarker or surrogate biomarker for recurrent spontaneous abortions. © 2012 British Society for Immunology. |
| format |
JOUR |
| author |
Fraccaroli, L. Grasso, E. Hauk, V. Cortelezzi, M. Calo, G. Pérez Leirós, C. Ramhorst, R. |
| author_facet |
Fraccaroli, L. Grasso, E. Hauk, V. Cortelezzi, M. Calo, G. Pérez Leirós, C. Ramhorst, R. |
| author_sort |
Fraccaroli, L. |
| title |
Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental-maternal leucocyte interaction impair the maternal tolerogenic response |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_00099104_v170_n3_p310_Fraccaroli |
| work_keys_str_mv |
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