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Abstract:

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.

Registro:

Documento: Artículo
Título:Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental-maternal leucocyte interaction impair the maternal tolerogenic response
Autor:Fraccaroli, L.; Grasso, E.; Hauk, V.; Cortelezzi, M.; Calo, G.; Pérez Leirós, C.; Ramhorst, R.
Filiación:Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires and National Research Council (IQUIBICEN-CONICET), Buenos Aires, Argentina
Argentinean Society of Gynecological and Endocrinological Reproduction, Buenos Aires, Argentina
Palabras clave: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
Año:2012
Volumen:170
Número:3
Página de inicio:310
Página de fin:320
DOI: http://dx.doi.org/10.1111/j.1365-2249.2012.04668.x
Título revista:Clinical and Experimental Immunology
Título revista abreviado:Clin. Exp. Immunol.
ISSN:00099104
CODEN:CEXIA
CAS:vasoactive intestinal polypeptide, 37221-79-7; Inflammation Mediators; Receptors, Vasoactive Intestinal Peptide; T-Box Domain Proteins; T-box transcription factor TBX21; Vasoactive Intestinal Peptide, 37221-79-7
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00099104_v170_n3_p310_Fraccaroli

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Citas:

---------- APA ----------
Fraccaroli, L., Grasso, E., Hauk, V., Cortelezzi, M., Calo, G., Pérez Leirós, C. & Ramhorst, R. (2012) . Defects in the vasoactive intestinal peptide (VIP)/VPAC system during early stages of the placental-maternal leucocyte interaction impair the maternal tolerogenic response. Clinical and Experimental Immunology, 170(3), 310-320.
http://dx.doi.org/10.1111/j.1365-2249.2012.04668.x
---------- CHICAGO ----------
Fraccaroli, L., Grasso, E., Hauk, V., Cortelezzi, M., Calo, G., Pérez Leirós, C., 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" . Clinical and Experimental Immunology 170, no. 3 (2012) : 310-320.
http://dx.doi.org/10.1111/j.1365-2249.2012.04668.x
---------- MLA ----------
Fraccaroli, L., Grasso, E., Hauk, V., Cortelezzi, M., Calo, G., Pérez Leirós, C., 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" . Clinical and Experimental Immunology, vol. 170, no. 3, 2012, pp. 310-320.
http://dx.doi.org/10.1111/j.1365-2249.2012.04668.x
---------- VANCOUVER ----------
Fraccaroli, L., Grasso, E., Hauk, V., Cortelezzi, M., Calo, G., Pérez Leirós, C., 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. Clin. Exp. Immunol. 2012;170(3):310-320.
http://dx.doi.org/10.1111/j.1365-2249.2012.04668.x