Reproductive BioMedicine Online
Volume 21, Issue 3 , Pages 304-311 , September 2010

New target cells of the immunomodulatory effects of progesterone

  • Dobroslav Kyurkchiev

      Affiliations

    • Laboratory of Clinical Immunology, University Hospital ‘St. Ivan Rilski’, Medical University Sofia, 15 Acad. Ivan Geshov, 1431 Sofia, Bulgaria
    • Corresponding Author InformationCorresponding author.
    • ,
  • Ekaterina Ivanova-Todorova

      Affiliations

    • Laboratory of Clinical Immunology, University Hospital ‘St. Ivan Rilski’, Medical University Sofia, 15 Acad. Ivan Geshov, 1431 Sofia, Bulgaria
    • ,
  • Stanimir Dobrev Kyurkchiev

      Affiliations

    • Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 73 Tzarigradsko Shosse, 1113 Sofia, Bulgaria

Received 15 December 2009 ,Revised 1 April 2010 ,Accepted 7 April 2010.

References 

  1. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105:1815–1822
  2. Aplin JD. Adhesion molecules in implantation. Rev. Reprod. 1997;2:84–112
  3. Askelund K, Liddell HS, Zanderigo AM, et al. CD83+ dendritic cells in the decidua of women with recurrent miscarriage and normal pregnancy. Placenta. 2004;25:140–145
  4. Bainbridge DRJ, Ellis SA, Sargent IL. HLA-G suppresses proliferation of CD4+ T-lymphocytes. J. Reprod. Immunol. 2000;48:17–26
  5. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–252
  6. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Hematol. 2002;30:42–48
  7. Bianco P, Gehron P, Robey P. Marrow stromal stem cells. J. Clin. Invest. 2000;105:1663–1668
  8. Blanco O, Tirado I, Munoz-Fernandez R, et al. Human decidual stromal cells express HLA-G effects of cytokines and decidualization. Hum. Reprod. 2008;23:144–152
  9. Blaschitz A, Lenfant F, Mallet V, et al. Endothelial cells in chorionic fetal vessels of first trimester placenta express HLA-G. Eur. J. Immunol. 1997;27:3380–3386
  10. Blois S, Zenclussen AC, Roux ME, et al. Asymmetric antibodies (AAb) in female reproductive tract. J. Reprod. Immunol. 2004;64:31–43
  11. Bochev I, Elmadjian G, Kyurkchiev D, et al. Mesenchymal stem cells from human bone marrow or adipose tissue differently modulate mitogen-stimulated B-cell immunoglobulin production in vitro. Cell Biol. Int. 2008;32:384–393
  12. Bromberg J, Fan Z, Brown S, Mendelsonh J, Darnell J. Epidermal growth factor-induced growth inhibition requires Stat1 activation. Cell Growth Differ. 1998;9:505–512
  13. Buelens C, Verhasselt V, De Groote D, Thielemans K, Goldman M, Willims F. Human dendritic cells responses to lipopolysaccharide and CD40 ligand are differentially regulated by interleukin 10. Eur. J. Immunol. 1997;27:1848–1852
  14. Canellada A, Blois S, Gentile T, Margni RA. In vitro modulation of protective antibody responses by estrogen, progesterone and interleukin-6. Am. J. Reprod. Immunol. 2002;48:334–343
  15. Chaouat G, Menu E, Delage G, Moreau JF, Khrishnan L, Hui Lin, et al. Immuno-endocrine interactions in early pregnancy. Hum. Reprod. 1995;10:55–58
  16. Chu W, Fant ME, Geraghty DE, Hunt JS. Soluble HLA-G in human placentas: synthesis in trophoblasts and interferon-g-activated macrophages but not placental fibroblasts. Hum. Immunol. 1998;59:435–442
  17. Curry TE, Osteen KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr. Rev. 2003;24:428–465
  18. Dai D, Wolf DM, Litman ES, White MJ, Leslie KK. Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res. 2002;62:881–886
  19. Darmochwal-Kolarz D, Rolinski J, Tabarkiewicz J, et al. Blood myeloid and lymphoid dendritic cells are stable during the menstrual cycle but deficient during mid-gestation. J. Reprod. Immunol. 2003;59:193–203
  20. Darmochwal-Kolarz D, Rolinski J, Tabarkiewicz J, et al. CD11c+ immature myeloid dendritic cells are predominant in cord blood of healthy neonates. IMLET. 2003;3866:1–4
  21. De Smedt T, Van Mechelen M, De Becker G, Urbain J, Leo O, Moser M. Effect of interleukin 10 on dendritic cell maturation and function. Eur. J. Immunol. 1997;27:1229–1235
  22. Derrien M, Pizzato N, Dolcini G, et al. Human immunodeficiency virus 1 downregulates cell surface expression of the non-classical major histocompatibility class I molecule HLA-G1. J. Gen. Virol. 2004;85:1945–1954
  23. Di Nicola M, Carlo-Stella C, Magni M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838–3843
  24. Dimitrov R, Timeva T, Kyurkchiev D, et al. Characterization of clonogenic stromal cells isolated from human endometrium. Reproduction. 2008;135:551–558
  25. Dimitrov R, Kyurkchiev D, Timeva T, et al. First-trimester human decidua contains a population of mesenchymal stem cells. Fertil. Steril. 2008;
  26. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–317
  27. Dosiou Ch, Giudice L. Neural killer cells in pregnancy and recurrent pregnancy loss: endocrine and immunologic perspectives. Endocr. Rev. 2005;261:44–62
  28. Fournel S, Aguerre-Girr M, Huc X, et al. Soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8+. J. Immunol. 2000;164:6100–6104
  29. Frucht DM. IL-23: a cytokine that acts on memory T cells. Sci. STKE. 2002;114:1
  30. Gargett CE. Uterine stem cells: what is the evidence?. Hum. Reprod. Update. 2007;13:87–101
  31. Gentile T, Margni RA. IgG asymmetric anti-ovalbumin antibodies synthesized by virgin and pregnant rats. J. Reprod. Immunol. 1995;28:1–13
  32. Geraghty DE, Koller BH, Orr HT. A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment. Proc. Natl. Acad. Sci. USA. 1987;84:9145–9149
  33. Hart D. Dendritic cells: unique leukocyte populations which control the primary immune response. Blood. 1997;90:3245–3287
  34. Han K, Lee JE, Kwon SJ, et al. Human amnion-derived mesenchymal stem cells are a potential source for uterine stem cell therapy. Cell Prolif. 2008;41(5):709–725
  35. Ivanova E, Kyurkchiev D, Altankova I, Dimitrov J, Binakova E, Kyurkchiev S. CD83+ monocyte-derived dendritic cells are present in human decidua and progesterone induces their differentiation in vitro. Am. J. Reprod. Immunol. 2005;53:199–205
  36. Ivanova-Todorova E, Kyurkchiev D, Mehandjiev T, Chernev T, Kyurkchiev S. Influence of progesterone on asymmetric antibodies synthesis in vitro. C. R. Acad. Bulg. Sci. 2008;61:1475–1480
  37. Ivanova-Todorova E, Mourdjeva M, Kyurkchiev D, et al. HLA-G expression is up-regulated by progesterone in mesenchymal stem cells. Am. J. Reprod. Immunol. 2009;62:25–33
  38. Ivanova-Todorova E, Kyurkchiev D, Mourdjeva M, et al. Pre-decidual multipotent stromal cells (preD-MSC) constitutively express progesterone induced blocking factor (PIBF). C. R. Bulg. Sci. 2009;62(12):1567–1570
  39. Jiang Y, Jahagirdar BN, Reinhardt RL. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41–49
  40. Kammerer U, Schoppet M, McLellan AD, Kapp M, Huppertz H-I, Kampgen E, et al. Human decidua contains potent immunostimulatory CD83+ dendritic cells. Am. J. Pathol. 2000;157:159–169
  41. Kato K, Yoshimoto M, Kato K, et al. Characterization of side-population cells in human normal endometrium. Hum. Reprod. 2007;22:1214–1223
  42. Kestendjieva S, Kyurkchiev D, Tsvetkova G, et al. Characterization of mesenchymal stem cells isolated from human umbilical cord. Cell Biol. Int. 2008;32:724–732
  43. Krampera M, Glennie S, Dyson J. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 2003;101:3722–3729
  44. Kozma N, Halasz M, Polgar B, et al. Progesterone-induced blocking factor activates STAT6 via binding to a novel IL-4 receptor. J. Immunol. 2006;176:819–826
  45. Kyurkchiev D, Ivanova-Todorova E, Hayrabedyan S, Altankova I, Kyurkchiev S. Female sex steroid hormones modify some regulatory properties of monocyte-derived dendritic cells. Am. J. Reprod. Immunol. 2007;58:425–433
  46. Kyurkchiev D, Ivanova-Todorova E, Altunkova I. Progesterone increases apoptosis and interleukin 10 secretion by mature monocyte derived dendritic cells. Biotechnol. Biotechnol. Equip. 2007;21:468–470
  47. Lafon M, Prehaud C, Megret F, et al. Modulation of HLA-G expression in human neural cells after neurotropic viral infections. J. Virol. 2005;79:15226–15237
  48. Langrish CL, Chen Y, Blumenschein MW, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. JEM. 2003;201:233–240
  49. Lankford CS, Frucht DM. A unique role for IL-23 in promoting cellular immunity. J. Leukoc. Biol. 2003;73:49–56
  50. Lea RG, Sandra O. Immunoendocrine aspects of endometrial function and implantation. Reproduction. 2007;134:389–404
  51. Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439–1441
  52. Le Bouteiller P. HLA class I chromosomal region, genes, and products: facts and questions. Crit. Rev. Immunol. 1994;14:89–105
  53. Le Bouteiller P, Solier C, Proll J, Aguerre-Girr M, Fournel S, Lenfant F. The major histocompatibility complex in pregnancy: Part II. Placental HLA-G protein expression in vivo: where and what for?. Hum. Reprod. Update. 1999;5:223–233
  54. Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG. Synthesis of T helper 2-type cytokines at the maternal–fetal interface. J. Immunol. 1993;151:4562–4573
  55. Mallet V, Blaschitz A, Crisa L, et al. HLA-G in the human thymus: a subpopulation of medullary epithelial but not CD83+ dendritic cells expresses HLA-G as a membrane-bound and soluble protein. Int. Immunol. 1999;11:889–898
  56. Marchal-Bras-Goncalves R, Rouas-Freiss N, Connan F, et al. A soluble HLA-G protein that inhibits natural killer cell-mediated cytotoxicity. Transplant. Proc. 2001;33:2355–2359
  57. Matthiesen L, Khademi M, Ekerfeld Ch, et al. In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy. JRI. 2003;58:49–59
  58. McMaster MT, Librach CL, Zhou Y. Human placental HLA-G expression is restricted to differentiated cytotrophoblasts. J. Immunol. 1995;154:3771–3778
  59. McMurray RW. Estrogen, prolactin and autoimmunity: actions and interactions. A review. Int. Immunopharmacol. 2001;1:995–1008
  60. Minguell JJ, Erices A. Mesenchymal stem cells and the treatment of cardiac disease. Exp. Biol. Med. 2006;231:39–49
  61. Miyayra H, Iwata M. Direct and indirect inhibition of Th1 development by progesterone and glucocorticoids. J. Immunol. 2002;168:1087–1094
  62. Movagar B, Tiraihi T, Mesbah-Namin . Transdifferentiation of bone marrow stromal stem cells into Schwann cell phenotype using progesterone as inducer. Brain Res. 2008;1208:17–24
  63. Owaki T, Asakawa M, Kamiya S, et al. IL-27 suppress CD28-mediated IL-2 production through suppressor of cytokine signaling. J. Immunol. 2006;176:2773–2780
  64. Piccinni MP, Scaletti C, Maggi E, Romagnani S. Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J. Neuroimmunol. 2000;109:30–33
  65. Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res. 2004;95:9–20
  66. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of human mesenchymal stem cells. Science. 1999;284:143–147
  67. Polgar B, Barankonyi A, Xynos I, Szekere-Bartho J. The role of gamma/delta T cell receptor positive cells in pregnancy. Am. J. Reprod. Immunol. 1999;41:239–244
  68. Polgar B, Kispal G, Lachmann M, et al. Molecular cloning and immunologic characterization of a novel cDNA coding for progesterone-induced blocking factor. J. Immunol. 2003;171:5956–5963
  69. Rasmusson I. Immune modulation by mesenchymal stem cells. Exp. Cell Res. 2006;312:2169–2179
  70. Sallusto F, Lanzaveccia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony stimulating factor plus interleukin 4 and down regulated by tumor necrosis factor-a. J. Exp. Med. 1994;179:1109–1118
  71. Sheshgiri R, Rao V, Tumiati LC, et al. Progesterone induces human leukocyte antigen-G expression in vascular endothelial and smooth muscle cells. Circulation. 2008;118:58–64
  72. Schimacher M, Coirin H, Robert F, Guennoun R, Eli-Etr M. Genomic and membrane actions of progesterone: implications for reproductive physiology and behaviour. Behavioural. Brain Res. 1999;105:37–52
  73. Schmidt M, Lugering N, Pauels HG, Schulze-Osthoff K, Domschke W, Kucharzik T. IL-10 Induces apoptosis in human monocytes involving the CD95 receptor/ligand pathway. Eur. J. Immunol. 2000;6:1769–1777
  74. Szekeres-Bartho J, Hadnagy J, Pacsa AS. The suppressive effect of progesterone on lymphocyte cytotoxicity: unique progesterone sensitivity of pregnancy lymphocytes. J. Reprod. Immunol. 1985;7:121–128
  75. Szekeres-Bartho J, Faust Z, Varga P. The expression of a progesterone-induced immunomodulatory protein in pregnancy lymphocytes. Am. J. Reprod. Immunol. 1995;34:342–348
  76. Szekeres-Bartho J, Balasch J. Progestogen therapy for recurrent miscarriage. Hum. Reprod. Update. 2008;14:27–35
  77. Torres MI, Lopez-Casado MA, Luque J, Pena J, Rıos A. New advances in coeliac disease: serum and intestinal expression of HLA-G. Int. Immunol. 2006;18:713–718
  78. Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur. J. Immunol. 2006;36:2566–2573
  79. Urosevic M, Willers J, Mueller B, Kempf W, Burg G, Dummer R. HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas. Blood. 2002;99:609–617
  80. Vegeto E, Pollio G, Pellicari C, Maggi A. Estrogen and progesterone induction of survival of monoblastoid cells undergoing TNF-a-induced apoptosis. FASEB J. 1999;13:793–803
  81. Verthelyi D. Sex hormones as immunomodulators in health and disease. Int. Immunopharmacol. 2001;1:983–993
  82. Wiendl H, Mitsdoerffer M, Hofmeister V, et al. A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. J. Immunol. 2002;168:4772–4780
  83. Wolff EF, Wolff AB, Du H, Taylor HS. Demonstration of multipotent stem cells in the adult human endometrium by in vitro chondrogenesis. Reprod. Sci. 2007;14(6):524–533
  84. Yang Y, Chu W, Geraghty DE, Hunt JS. Expression of HLA-G in human mononuclear phagocytes and selective induction by IFN-gamma. J. Immunol. 1996;156:4224–4231
  85. Yie S, Li L, Li G, Xiao R, Librach CL. Progesterone enhances HLA-G gene expression in JEG-3 choriocarcinoma cells and human cytotrophoblasts in vitro. Hum. Reprod. 2006;21:46–51
  86. Yoshimura T, Inaba M, Sugiura K, Nakajima T, Ito T, Nakamura K, et al. Analysis of dendritic cell subsets in pregnancy. AJRI. 2003;50:137–145
  87. Zhoe LJ, Tedder TF. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc. Natl. Acad. Sci. USA. 1996;93:2588–2592

 Dr Dobroslav Kyurkchiev graduated from the Medical University in Sofia, Bulgaria with his MD and in 2003 he gained his PhD in clinical immunology. Since 2004, he has been working in the Department of Clinical Laboratory and Clinical Immunology, Medical University, Sofia. Dr Kyurkchiev has successfully researched the participation of the immune cells in the pathogenesis of the antiphospholipid syndrome and particularly the cellular immune response against β2-glycoprotein I. Currently he is researching the effect of reproductive steroid hormones on cells that are actively engaged in the control of the immune response in pregnancy.

PII: S1472-6483(10)00226-9

doi: 10.1016/j.rbmo.2010.04.014

Reproductive BioMedicine Online
Volume 21, Issue 3 , Pages 304-311 , September 2010

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