调节性T细胞与Th17细胞动态平衡参与母-胎免疫调节的分子机制

The success of pregnancy should be considered as a case of successful allograft, and it is also a remarkable exception against immunological principles. Therefore, the failure outcome of pregnancy means maternal rejection to fetus from the perspective of immunology. In our previous studies, it had been shown that trophoblast cells could educate decidual dendritic cells(DCs) by secreting TSLP, leading to Th2 bias at the maternal-fetal interface, and make local decidual T cells differentiate into regulatory T cells, thus contributing to the maternal-fetal immune tolerance. Recent studies show that during pregnancy, decidual regulatory T cells and Th17 cells were significantly expanded. However, whether these two groups of Th cells participate in the maternal-fetal immune regulation and mediate maternal-fetal immune tolerance through synergistic or antagonistic ways still remains fully elucidated. Our subject here focuses on the important roles regulatory T cells and Th17 cells play respectively and cooperatively during pregnancy. By establishing cell co-culture system and the CD4+ T cell inducing differentiation system, etc., we will study the differentiation and developmental process of these two groups of cells and their regulatory function at maternal-fetal interface. This work will develop and complement immune tolerance theory, hence will be a breakthrough in maternal-fetal immunoregulatory theory, thus contributing to transplantation immunology, tumor immunology, pathogenesis of autoimmune diseases and leading to new preventive strategies.

成功妊娠是同种异体移植物及其免疫学原理的唯一例外；妊娠失败意味着母体免疫系统对同种移植物胚胎免疫排斥。我们前期研究发现滋养细胞分泌TSLP，训导蜕膜DC细胞，使母胎界面呈现Th2型免疫优势，并驱使蜕膜局部T细胞分化发育成调节性 T细胞，有利于母胎免疫耐受的形成。最近研究显示妊娠期蜕膜局部调节性T细胞及Th17细胞均明显扩增；这两群Th细胞是否通过协同或拮抗作用，参与母胎免疫调节，并介导母胎免疫耐受，至今尚未充分阐明。本课题拟以妊娠期调节性T细胞与Th17细胞单独作用及复合作用为切入口，通过细胞共培养、建立CD4T细胞分化诱导体系，研究这两群细胞分化发育调节过程及其对母胎界面关键的功能细胞的调节作用，以解析其在母胎免疫调节及母胎免疫耐受中的作用机制，使母－胎免疫调节理论取得突破性进展，丰富和发展免疫生物学领域免疫耐受理论；并促进移植免疫学、肿瘤免疫学及自身免疫性疾病发病机制及防治新策略。

我们的研究结果显示：母-胎界面存在naïve CD4+ T细胞。滋养细胞、DSC分别，或两者共培养均显著抑制蜕膜naïve CD4+ T细胞分化发育为Th17细胞。用母-胎界面主要功能细胞条件培养液处理蜕膜naïve CD4+ T细胞显示，母-胎界面主要功能细胞条件培养液可显著抑制Th17细胞的分化，促进Treg细胞的优势分化。妊娠相关激素不影响Th17细胞的分化。因此，母-胎界面微环境有利于naïve CD4+ T细胞分化发育为Treg细胞，而不利于分化发育为Th17细胞，呈现Treg偏移。