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Immunological roles of human leukocyte antigens (HLA) expressed on the trophoblasts in maintaining pregnancy.

Research Project

Project/Area Number 13671698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionThe University of Tokyo

Principal Investigator

FUJII Tomoyuki  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (40209010)

Co-Investigator(Kenkyū-buntansha) KOZUMA Shiro  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (10272569)
三木 明徳  東京大学, 医学部附属病院, 助手 (50316767)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsHLA-E / HLA-G / Herbal medicine / Cytokine / Cell culture / Trophoblast / Pregnancy / Immunology / 脱落膜 / リンパ球 / ナチュラルキラー活性 / 漢方 / 習慣流産 / Decidua / Habitual Abortion / Herbal Medicine / Th1 Cytokine / Th2 Cytokine
Research Abstract

The object of this research project was to clarify the immunological roles of human leukocyte antigen (HLA) expressed on the trophoblasts to maintain pregnancy. We have performed 4 studies as follows.
1)Immunological roles of soluble HLA-G (sHLA-G) protein in maintaining pregnancy.
sHLA-G protein counterbalances membrane-bound HLA-G (mHLA-G) by shifting the balance of T helper (Th)1/Th2 cytokines secreted by peripheral mononuclear cells (PBMCs) to Thl polarization. However, sHLA-G protein modulated the release of cytokines from decidual mononuclear cells (DMCs) additively to mHLA-G by shifting-the Thl/Th2 balance to Th2 polarization.
SHLA-G did not affect the natural killer activity of PBMCs.
2)Immunological roles of HLA-E in maintaining pregnancy.
HLA-E suppressed the release of tumor necrosis factor (TNF)-α from PBMCs additively to mHLA-G but enhanced the release of interferon (IFN)-γ contrary to mHLA-G.
3)Effects of herbal medicines on the immune reaction of patients with autoimmunity related recurrent abortion.
Herbal medicines, Tokishakuyaku-san and Sairei-To, enhanced the secretion of Thi cytokines from PBMCs but (lid not affect the cytokine secretion from DMCs. These data provided the rationale of herbal medicines in the treatment of autoimmunity related recurrent abortion.
4)A primary cell culture system for human cytotrophoblasts.
We have established a novel cell culture system for highly purified human cytotrophoblasts enabling in vitro acquisition of extra-villous phenotype. The cultured trophoblasts gradually upregulated HLA-G along with the differentiation to extra-villous phenotype

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kanai T, 他: "A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear cells present in the decidua additively to membrane-bound HLA-G1."J Reprod Immunol. 60. 85-96 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 金井 孝夫 他: "Human leukocyte antigen(HLA)-Eが母体単核珠のサイトカイン産生に与える影響について:HLA-Gとの比較"日産婦誌. 55. 265-265 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii T, 他: "Herbal medicines, Sairei-to and Tokishakuyaku-san, differently modulate the release of cytokines from decidual versus peripheral blood mononuclear cells."Am J Reprod Immunol. 46. 369-372 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii T: "Herbal factors in the treatment of autoimmunity-related habitual abortion (Review)."Vitam Horm. 65. 334-344 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagamatsu T, 他: "A primary Cell Culture System for Human Cytotrophoblasts of Proximal Cytotrophoblast Cell Column Enabling In Vitro Acquisition of Extra-villous Phenotype."Placenta. 25. 153-165 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanai T, Fujii T, Kozuma S, Miki A, Yamashita T, Hyodo H, Unno N, Yoshida S, Taketani Y: "A subclass of soluble HLA-G1 modulates the release of cytokines from mononuclear cells present in the decidua additively to membrane-hound HLA-GI."J Reprod Immunol. 60(2). 85-96 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kanai T, Fujii T, Nagamatsu T, Hyodo H, Yamashita T, Kozuma S, Taketani Y: "HLA-E modulates the release of cytokines from peripheral blood mononuclear cells. Comparison to HLA-G [Japanese]."Nippon Sanka Fujinka Gakkai Zasshi. 55(2). 265-265 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii T, Kanai T, Kozuma S, Baba K, Miki A, Hyodo H, Yamashita T, Unno N, Taketani Y: "Herbal medicines, Sairei-to and Tokishakuyaku-san, differently modulate the release of cytokines from decidual versus peripheral blood mononuclear cells."Am J Reprod Immunol. 46(5). 369-372 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii T: "Herbal factors in the treatment of autoimmunity-related habitual abortion (Review)."Vitam Horm. 65. 334-344 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagamatsu T, Fujii T, Ishikawa T, Kanai T, Hyodo H, Yamashita T, Osuga Y,. Momoeda M, Kozuma S, Taketani Y: "A Primary cell culture system for human cytotrophoblasts of Pproximal cytotrophoblast cell column enabling in vitro acquisition of extra-villous phenotype."Placenta. 25(2-3). 153-165 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagamatsu 他: "A Primary Cell Culture System for Human Cytotrophoblasts of Proximal Cytotrophoblast Cell Columns Enabling In Vitro Acquisition of the Extra-vinous Phenotype."Placenta. 25・2-3. 153-165 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomoyuki Fujii: "Herbal factors in the treatment of autoimmunity-related habitual abortion"Vitamins and Hormones. 65. 333-344 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanai T, et al.: "Soluble human leukocyte antigen(HLA)-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture"Mol Hum Reprod. 7. 195-200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanai T, et al.: "Polymorphism of human leukocyte antigen(HLA)-E gene in Japanese population with or without recurrent abortion"Am J Reprod Immunol. 45. 168-173 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujii T, et al.: "Herbal medicines, Sairei-to and Tokishakuyaku-san, differently modulate the release of cytokines from decidual versus peripheral blood mononuclear cells"Am J Reprod Immunol. 46. 369-372 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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