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

滋养细胞上表达的人类白细胞抗原（HLA）在维持妊娠中的免疫学作用。

• 批准号: 13671698
• 负责人: FUJII Tomoyuki
• 金额: $ 2.37万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671698/
• 关键词: HLA-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

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

本研究的目的是阐明滋养层细胞表达的人类白细胞抗原（HLA）在维持妊娠中的免疫学作用。本研究主要做了以下四个方面的研究：1）可溶性HLA-G（sHLA-G）蛋白在维持妊娠中的免疫学作用：sHLA-G蛋白通过改变外周血单个核细胞（PBMC）分泌的Th_1/Th_2细胞因子的平衡，使Th_1极化，从而平衡膜结合的HLA-G（mHLA-G）。然而，在这方面，2）HLA-E在维持妊娠中的免疫作用：HLA-E抑制PBMC释放肿瘤坏死因子（TNF）-α，促进IFN-γ的释放，但不影响PBMC的自然杀伤活性。3）中药对自身免疫相关性复发性流产患者免疫反应的影响：中药常侍和西令藤能促进PBMC分泌Thi细胞因子，但对DMCs分泌Thi细胞因子无影响。这些结果为中药治疗自身免疫性复发性流产提供了理论依据。4）人细胞滋养层细胞的原代培养体系我们建立了一种新的高纯度人细胞滋养层细胞的培养体系，使其能够在体外获得绒毛外表型。随着滋养细胞向绒毛外表型的分化，HLA-G的表达沿着上调

项目成果

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)

Fujii T 等人：“草药、Sairei-to 和 Tokishakuyaku-san 不同地调节蜕膜细胞和外周血单核细胞的细胞因子释放。”Am J Reprod Immunol. 46. 369-372 (2001)

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 p

Nagamatsu T、Fujii T、Ishikawa T、Kanai T、Hyodo H、Yamashita T、Osuga Y，。

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)

Kanai T 等人：“可溶性 HLA-G1 的一个亚类除了膜结合的 HLA-G1 之外还调节蜕膜中单核细胞的细胞因子释放。”J Reprod Nutrition 60. 85-96 (2003)

Fujii T: "Herbal factors in the treatment of autoimmunity-related habitual abortion (Review)."Vitam Horm. 65. 334-344 (2002)

Fujii T：“治疗自身免疫相关习惯性流产的草药因素（综述）。”Vitam Horm。

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)

Fujii T 等人：“草药，Sairei-to 和 Tokishakuyaku-san，以不同方式调节蜕膜细胞与外周血单核细胞的细胞因子释放”Am J Reprod Immunol。