title: Elevated levels of dehydroepiandrosterone as a potential mechanism of dendritic cell impairment during pregnancy.
abstract: BACKGROUND
  This study aimed to test the hypothesis that immune dysfunction and the increased risk of spontaneous abortion in pregnant women with hyperandrogenia (HA) are caused by the reduced tolerogenic potential of dendritic cells (DCs) that results from elevated levels of dehydroepiandrosterone sulfate (DHEAS).
  
  
  METHODS
  The phenotypic and functional properties of monocyte-derived DCs generated from blood monocytes from non-pregnant women, women with a normal pregnancy, or pregnant women with HA, as well as the in vitro effects of DHEAS on DCs in healthy pregnant women were investigated.
  
  
  RESULTS
  In a normal pregnancy, DCs were shown to be immature and are characterized by a reduced number of CD83(+) and CD25(+) DCs, the ability to stimulate type 2 T cell responses and to induce T cell apoptosis. By contrast, DCs from pregnant women with HA had a mature phenotype, were able to stimulate both type 1 (IFN-γ) and type 2 (IL-4) T cell responses, and were characterized by lower B7-H1 expression and cytotoxic activity against CD8(+) T cells. The addition of DHEAS to cultures of DCs from healthy pregnant women induced the maturation of DCs and increased their ability to activate type 1 T cell responses.
  
  
  CONCLUSIONS
  Our data demonstrated the reduction in the tolerogenic potential of DCs from pregnant women with HA, and revealed new mechanisms involved in the hormonal regulation of DCs mediated by DHEAS.
authors: Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya St., 630099, Novosibirsk, Russia. ct_lab@mail.ru.
authors: Elena R
authors: ER
authors: Chernykh
authors: Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya St., 630099, Novosibirsk, Russia. oleplina@mail.ru.
authors: Olga Yu
authors: OY
authors: Leplina
authors: Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya St., 630099, Novosibirsk, Russia. matrix-59@mail.ru.
authors: Marina A
authors: MA
authors: Tikhonova
authors: Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya St., 630099, Novosibirsk, Russia. jewel82@mail.ru.
authors: Nataliya V
authors: NV
authors: Seledtsova
authors: Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya St., 630099, Novosibirsk, Russia. tyrinova@mail.ru.
authors: Tamara V
authors: TV
authors: Tyrinova
authors: Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya St., 630099, Novosibirsk, Russia. nkhonina@mail.ru.
authors: Nataliya A
authors: NA
authors: Khonina
authors: Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, 14, Yadrintsevskaya St., 630099, Novosibirsk, Russia. ostanin62@mail.ru.
authors: Alexandr A
authors: AA
authors: Ostanin
authors: Novosibirsk State University, 2, Pirogova St., 630090, Novosibirsk, Russia. pasman@mail.ru.
authors: Nataliya M
authors: NM
authors: Pasman
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology*; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000276:immunology*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D011247:Pregnancy; D012306:Risk; D018417:Th1 Cells / Q000276:immunology*; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D015847:Interleukin-4; D003687:Dehydroepiandrosterone; D007371:Interferon-gamma
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