Navegar

Colección

Datos Estadísticas

Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

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.

Registro:

Documento: Artículo
Título:VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast–maternal leukocyte interaction
Autor:Fraccaroli, L.; Grasso, E.; Hauk, V.; Paparini, D.; Soczewski, E.; Mor, G.; Leirós, C.P.; Ramhorst, R.
Filiación:Laboratory of Immunopharmacology, University of Buenos Aires School of Sciences, IQUIBICEN–CONICET (National Research Council), Buenos Aires, Argentina
Reproductive Immunology Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, United States
University of Buenos Aires School of Medicine, Buenos Aires, Argentina
Palabras clave:Early pregnancy; iTreg; TGF-β; Tolerance; CD4 antigen; gamma interferon; interleukin 10; interleukin 17; polypeptide; transcription factor FOXP3; transforming growth factor beta; transforming growth factor beta antibody; vasoactive intestinal polypeptide; vasoactive intestinal polypeptide antagonist; vasoactive intestinal polypeptide receptor; interleukin 10; transforming growth factor beta1; vasoactive intestinal polypeptide; Article; cell interaction; cell population; cell suspension; coculture; controlled study; cytokine production; DNA cross linking; DNA synthesis; female; first trimester pregnancy; human; human cell; immune response; in vitro study; intracellular space; leukocyte; peripheral blood mononuclear cell; priority journal; regulatory T lymphocyte; trophoblast; biosynthesis; cell communication; cell line; cytology; drug effects; immunology; leukocyte; metabolism; pregnancy; real time polymerase chain reaction; regulatory T lymphocyte; trophoblast; Cell Communication; Cell Line; Coculture Techniques; Female; Humans; In Vitro Techniques; Interleukin-10; Leukocytes; Pregnancy; Pregnancy Trimester, First; Real-Time Polymerase Chain Reaction; T-Lymphocytes, Regulatory; Transforming Growth Factor beta1; Trophoblasts; Vasoactive Intestinal Peptide
Año:2015
Volumen:98
Número:1
Página de inicio:49
Página de fin:58
DOI: http://dx.doi.org/10.1189/jlb.1A1014-492RR
Título revista:Journal of Leukocyte Biology
Título revista abreviado:J. Leukocyte Biol.
ISSN:07415400
CODEN:JLBIE
CAS:gamma interferon, 82115-62-6; vasoactive intestinal polypeptide, 37221-79-7; Interleukin-10; Transforming Growth Factor beta1; Vasoactive Intestinal Peptide
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07415400_v98_n1_p49_Fraccaroli

Referencias:

  • Mor, G., Cardenas, I., The immune system in pregnancy: A unique complexity (2010) Am. J. Reprod. Immunol., 63, pp. 425-433
  • Dekel, N., Gnainsky, Y., Granot, I., Mor, G., Inflammation and implantation (2010) Am. J. Reprod. Immunol., 63, pp. 17-21
  • Moser, G., Gauster, M., Orendi, K., Glasner, A., Theuerkauf, R., Huppertz, B., Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models (2010) Hum. Reprod., 25, pp. 1127-1136
  • Weiss, G., Goldsmith, L.T., Taylor, R.N., Bellet, D., Taylor, H.S., Inflammation in reproductive disorders (2009) Reprod. Sci., 16, pp. 216-229
  • Guerin, L.R., Prins, J.R., Robertson, S.A., Regulatory T-cells and immune tolerance in pregnancy: A new target for infertility treatment? (2009) Hum. Reprod. Update, 15, pp. 517-535
  • Aluvihare, V.R., Kallikourdis, M., Betz, A.G., Regulatory T cells mediate maternal tolerance to the fetus (2004) Nat. Immunol., 5, pp. 266-271
  • Gomez-Lopez, N., Guilbert, L.J., Olson, D.M., Invasion of the leukocytes into the fetal-maternal interface during pregnancy (2010) J. Leukoc. Biol., 88, pp. 625-633
  • Chaouat, G., Petitbarat, M., Dubanchet, S., Rahmati, M., Ledée, N., Tolerance to the foetal allograft? (2010) Am. J. Reprod. Immunol., 63, pp. 624-636
  • Yoshinaga, K., Research on blastocyst implantation essential factors (BIEFs) (2010) Am. J. Reprod. Immunol., 63, pp. 413-424
  • Molvarec, A., Blois, S.M., Stenczer, B., Toldi, G., Tirado-Gonzalez, I., Ito, M., Shima, T., Saito, S., Peripheral blood galectin-1-expressing T and natural killer cells in normal pregnancy and preeclampsia (2011) Clin. Immunol., 139, pp. 48-56
  • Blois, S.M., Ilarregui, J.M., Tometten, M., Garcia, M., Orsal, A.S., Cordo-Russo, R., Toscano, M.A., Arck, P.C., A pivotal role for galectin-1 in fetomaternal tolerance (2007) Nat. Med., 13, pp. 1450-1457
  • Saito, S., Nakashima, A., Shima, T., Ito, M., Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy (2010) Am. J. Reprod. Immunol., 63, pp. 601-610
  • Samy, E.T., Setiady, Y.Y., Ohno, K., Pramoonjago, P., Sharp, C., Tung, K.S.K., The role of physiological self-antigen in the acquisition and maintenance of regulatory T-cell function (2006) Immunol. Rev., 212, pp. 170-184
  • Zenclussen, A.C., Gerlof, K., Zenclussen, M.L., Sollwedel, A., Bertoja, A.Z., Ritter, T., Kotsch, K., Volk, H.D., Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: Adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model (2005) Am. J. Pathol., 166, pp. 811-822
  • Samstein, R.M., Josefowicz, S.Z., Arvey, A., Treuting, P.M., Rudensky, A.Y., Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict (2012) Cell, 150, pp. 29-38
  • Gobert, M., Lafaille, J.J., Maternal-fetal immune tolerance, block by block (2012) Cell, 150, pp. 7-9
  • Zheng, Y., Josefowicz, S., Chaudhry, A., Peng, X.P., Forbush, K., Rudensky, A.Y., Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate (2010) Nature, 463, pp. 808-812
  • Rudra, D., Egawa, T., Chong, M.M.W., Treuting, P., Littman, D.R., Rudensky, A.Y., Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells (2009) Nat. Immunol., 10, pp. 1170-1177
  • Kitoh, A., Ono, M., Naoe, Y., Ohkura, N., Yamaguchi, T., Yaguchi, H., Kitabayashi, I., Sakaguchi, S., Indispensable role of the Runx1-Cbfbeta transcription complex for in vivo-suppressive function of FoxP3+ regulatory T cells (2009) Immunity, 31, pp. 609-620
  • Gressens, P., Marret, S., Hill, J.M., Brenneman, D.E., Gozes, I., Fridkin, M., Evrard, P., Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain (1997) J. Clin. Invest., 100, pp. 390-397
  • Månsson, B., Nilsson, B.O., Ekström, J., Effects of repeated infusions of substance P and vasoactive intestinal peptide on the weights of salivary glands subjected to atrophying influences in rats (1990) Br. J. Pharmacol., 101, pp. 853-858
  • Ekström, J., Månsson, B., Tobin, G., Vasoactive intestinal peptide evoked secretion of fluid and protein from rat salivary glands and the development of supersensitivity (1983) Acta Physiol. Scand., 119, pp. 169-175
  • Roca, V., Larocca, L., Calafat, M., Aisemberg, J., Meiss, R., Franchi, A.M., Leirós, C.P., Reduced nitric oxide synthase and cyclo-oxygenase activity in the uterus of non-obese diabetic mice (2006) Reproduction, 132, pp. 931-938
  • Martinez, C., Delgado, M., Abad, C., Gomariz, R.P., Ganea, D., Leceta, J., Regulation of VIP production and secretion by murine lymphocytes (1999) J. Neuroimmunol., 93, pp. 126-138
  • Li, J.-M., Southerland, L., Hossain, M.S., Giver, C.R., Wang, Y., Darlak, K., Harris, W., Waller, E.K., Absence of vasoactive intestinal peptide expression in hematopoietic cells enhances Th1 polarization and antiviral immunity in mice (2011) J. Immunol., 187, pp. 1057-1065
  • Delgado, M., Abad, C., Martinez, C., Leceta, J., Gomariz, R.P., Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease (2001) Nat. Med., 7, pp. 563-568
  • Jovanovic, S., Grbovic, L., Jovanovic, A., Pregnancy does not alter the response of uterine arteries to vasoactive intestinal polypeptide (2000) Mol. Hum. Reprod., 6, pp. 361-368
  • Spong, C.Y., Lee, S.J., McCune, S.K., Gibney, G., Abebe, D.T., Alvero, R., Brenneman, D.E., Hill, J.M., Maternal regulation of embryonic growth: The role of vasoactive intestinal peptide (1999) Endocrinology, 140, pp. 917-924
  • Roca, V., Calafat, M., Larocca, L., Ramhorst, R., Farina, M., Franchi, A.M., Leirós, C.P., Potential immunomodulatory role of VIP in the implantation sites of prediabetic nonobese diabetic mice (2009) Reproduction, 138, pp. 733-742
  • Fraccaroli, L., Alfieri, J., Larocca, L., Calafat, M., Roca, V., Lombardi, E., Ramhorst, R., Leirós, C.P., VIP modulates the pro-inflammatory maternal response, inducing tolerance to trophoblast cells (2009) Br. J. Pharmacol., 156, pp. 116-126
  • Marzioni, D., Fiore, G., Giordano, A., Nabissi, M., Florio, P., Verdenelli, F., Petraglia, F., Castellucci, M., Placental expression of substance P and vasoactive intestinal peptide: Evidence for a local effect on hormone release (2005) J. Clin. Endocrinol. Metab., 90, pp. 2378-2383
  • Deutsch, P.J., Sun, Y., Kroog, G.S., Vasoactive intestinal peptide increases intracellular cAMP and gonadotropin-alpha gene activity in JEG-3 syncytial trophoblasts. Constraints posed by desensitization (1990) J. Biol. Chem., 265, pp. 10274-10281
  • Straszewski-Chavez, S.L., Abrahams, V.M., Alvero, A.B., Aldo, P.B., Ma, Y., Guller, S., Romero, R., Mor, G., The isolation and characterization of a novel telomerase immortalized first trimester trophoblast cell line, Swan 71 (2009) Placenta, 30, pp. 939-948
  • Pattillo, R.A., Gey, G.O., The establishment of a cell line of human hormone-synthesizing trophoblastic cells in vitro (1968) Cancer Res., 28, pp. 1231-1236
  • Kohler, P.O., Bridson, W.E., Isolation of hormone-producing clonal lines of human choriocarcinoma (1971) J. Clin. Endocrinol. Metab., 32, pp. 683-687
  • Schneider, C.A., Rasband, W.S., Eliceiri, K.W., NIH Image to ImageJ: 25 years of image analysis (2012) Nat. Methods, 9, pp. 671-675
  • Edelstein, A., Amodaj, N., Hoover, K., Vale, R., Stuurman, N., Computer control of microscopes using μManager (2010) Curr. Protoc. Mol. Biol., 14-20, pp. 14.20.1-14.20.17
  • Pozo, D., Anderson, P., Gonzalez-Rey, E., Induction of alloantigenspecific human T regulatory cells by vasoactive intestinal peptide (2009) J. Immunol., 183, pp. 4346-4359
  • Sakaguchi, S., Sakaguchi, N., Shimizu, J., Yamazaki, S., Sakihama, T., Itoh, M., Kuniyasu, Y., Takahashi, T., Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: Their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance (2001) Immunol. Rev., 182, pp. 18-32
  • Chen, W., Jin, W., Hardegen, N., Lei, K.-J., Li, L., Marinos, N., McGrady, G., Wahl, S.M., Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor FoxP3 (2003) J. Exp. Med., 198, pp. 1875-1886
  • Delgado, M., Munoz-Elias, E.J., Gomariz, R.P., Ganea, D., Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide prevent inducible nitric oxide synthase transcription in macrophages by inhibiting NF-kappa B and IFN regulatory factor 1 activation (1999) J. Immunol., 162, pp. 4685-4696
  • Gonzalez-Rey, E., Delgado, M., Vasoactive intestinal peptide and regulatory T-cell induction: A new mechanism and therapeutic potential for immune homeostasis (2007) Trends Mol. Med., 13, pp. 241-251
  • Leceta, J., Gomariz, R.P., Martinez, C., Carrión, M., Arranz, A., Juarranz, Y., Vasoactive intestinal peptide regulates Th17 function in autoimmune inflammation (2007) Neuroimmunomodulation, 14, pp. 134-138
  • Gonzalez-Rey, E., Anderson, P., Delgado, M., Emerging roles of vasoactive intestinal peptide: A new approach for autoimmune therapy (2007) Ann. Rheum. Dis., 66, pp. iii70-iii76
  • Chorny, A., Gonzalez-Rey, E., Fernandez-Martin, A., Ganea, D., Delgado, M., Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graftversus- tumor response (2006) Blood, 107, pp. 3787-3794
  • Toscano, M.G., Delgado, M., Kong, W., Martin, F., Skarica, M., Ganea, D., Dendritic cells transduced with lentiviral vectors expressing VIP differentiate into VIP-secreting tolerogenic-like DCs (2010) Mol. Ther., 18, pp. 1035-1045
  • Gonzalez-Rey, E., Ganea, D., Delgado, M., Neuropeptides: Keeping the balance between pathogen immunity and immune tolerance (2010) Curr. Opin. Pharmacol., 10, pp. 473-481
  • Robertson, S.A., Prins, J.R., Sharkey, D.J., Moldenhauer, L.M., Seminal fluid and the generation of regulatory T cells for embryo implantation (2013) Am. J. Reprod. Immunol., 69, pp. 315-330
  • Teles, A., Thuere, C., Wafula, P.O., El-Mousleh, T., Zenclussen, M.L., Zenclussen, A.C., Origin of Foxp3(+) cells during pregnancy (2013) Am J Clin Exp Immunol, 2, pp. 222-233
  • Teles, A., Zenclussen, A.C., Schumacher, A., Regulatory T cells are baby's best friends (2013) Am. J. Reprod. Immunol., 69, pp. 331-339
  • Klunker, S., Chong, M.M.W., Mantel, P.-Y., Palomares, O., Bassin, C., Ziegler, M., Rückert, B., Akdis, C.A., Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells (2009) J. Exp. Med., 206, pp. 2701-2715
  • 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 (2012) Clin. Exp. Immunol., 170, pp. 310-320
  • Pérez Leirós, C., Ramhorst, R., Tolerance induction at the early maternal-placental interface through selective cell recruitment and targeting by immune polypeptides (2013) Am. J. Reprod. Immunol., 69, pp. 359-368
  • Ramhorst, R., Fraccaroli, L., Aldo, P., Alvero, A.B., Cardenas, I., Leirós, C.P., Mor, G., Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells (2012) Am. J. Reprod. Immunol., 67, pp. 17-27
  • Nancy, P., Tagliani, E., Tay, C.-S., Asp, P., Levy, D.E., Erlebacher, A., Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface (2012) Science, 336, pp. 1317-1321
  • Obermajer, N., Popp, F.C., Soeder, Y., Haarer, J., Geissler, E.K., Schlitt, H.J., Dahlke, M.H., Conversion of Th17 into IL-17A(neg) regulatory T cells: A novel mechanism in prolonged allograft survival promoted by mesenchymal stem cell-supported minimized immunosuppressive therapy (2014) J. Immunol., 193, pp. 4988-4999

Citas:

---------- APA ----------
Fraccaroli, L., Grasso, E., Hauk, V., Paparini, D., Soczewski, E., Mor, G., Leirós, C.P.,..., Ramhorst, R. (2015) . VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast–maternal leukocyte interaction. Journal of Leukocyte Biology, 98(1), 49-58.
http://dx.doi.org/10.1189/jlb.1A1014-492RR
---------- CHICAGO ----------
Fraccaroli, L., Grasso, E., Hauk, V., Paparini, D., Soczewski, E., Mor, G., et al. "VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast–maternal leukocyte interaction" . Journal of Leukocyte Biology 98, no. 1 (2015) : 49-58.
http://dx.doi.org/10.1189/jlb.1A1014-492RR
---------- MLA ----------
Fraccaroli, L., Grasso, E., Hauk, V., Paparini, D., Soczewski, E., Mor, G., et al. "VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast–maternal leukocyte interaction" . Journal of Leukocyte Biology, vol. 98, no. 1, 2015, pp. 49-58.
http://dx.doi.org/10.1189/jlb.1A1014-492RR
---------- VANCOUVER ----------
Fraccaroli, L., Grasso, E., Hauk, V., Paparini, D., Soczewski, E., Mor, G., et al. VIP boosts regulatory T cell induction by trophoblast cells in an in vitro model of trophoblast–maternal leukocyte interaction. J. Leukocyte Biol. 2015;98(1):49-58.
http://dx.doi.org/10.1189/jlb.1A1014-492RR