Galectin9/Tim3相互作用调节蜕膜CD4+T细胞分化与功能的分子机制

成功妊娠依赖母体对胚胎抗原的免疫耐受，一旦母胎免疫调节异常将导致妊娠失败。我们前期发现，蜕膜局部Th2型优势与调节性T细胞扩增对正常妊娠维持至关重要，其机制仍不明确。T淋巴细胞免疫球蛋白黏蛋白家族分子Tim3在CD4+T细胞功能中发挥重要作用。最近我们发现Tim3及其配体Galectin9在人早孕自然流产滋养细胞表达较正常妊娠显著降低；Tim3在人早孕正常妊娠与自然流产蜕膜、外周血与蜕膜局部CD4+T细胞亚群差异表达，表明Tim3对蜕膜CD4+T细胞亚群表型与功能至关重要。本课题以正常妊娠与自然流产CD4+T细胞亚群差异表达Tim3为切入点，建立细胞共培养与CD4+T细胞分化诱导体系，解析Galectin9/Tim3在早孕蜕膜CD4+T细胞亚群分化与功能中的调节作用，阐明母胎免疫耐受机制，为母胎免疫调节紊乱性疾患的防治提供新策略。

The success of pregnancy depends on the tolerance of maternal immune system to embryonic antigens. The disregulation of maternal-fetal immune would result in pregnancy loss. We have reported that decidual Th2 bias and regulatory T cell expansion are crucial for successful pregnancy.The family of T cell immunoglobulin mucin (Tim) plays important roles in T cell tolerance. Our preliminary data show Tim-3 and its ligand galectin 9 are decreased in embryo trophoblasts and decidual stromal cells from unexplained miscarriage compared with that from normal pregnancy. The expression of Tim 3 in CD4+T subsets (Th1, Th2, Th17 and regulatory T cells) in normal pregnancy are also distinguished with that from unexplained miscarriage. These results suggest that Tim 3 signal is key in the maintenance of CD4+T cell function at the maternal-fetal interface. Our subject will study from the different expression of Tim 3 in human trophoblasts and immune cell subsets at the maternal-fetal interface. We will investigate the regulatory role of galectin 9/Tim 3 in the functional development of decidual CD4+T cells by using cell coculture and CD4+T cell differentiation systems, elucidating the mechanism of materno-fetal tolerance. This work will be helpful in the development of new preventive strategies in materno-fetal disorders such as spontaneous abortion and preeclampsia.