IL-33/ST2诱导早孕期蜕膜免疫细胞分化及其功能调控的分子机制

The crosstalk between DSCs, DICs and Tros at maternal-fetal interface during early pregnancy, which results in the differentiation and development of DICs and immune balance between Th1/Th2 and Th17/Treg, is the crucial factor for successful pregnancy. And exploring its underlying mechanism has become a hotspot and nodus on research of immune tolerance. IL-33 possess various immune regulation effects, and its receptor is widely expressed on many kinds of immune cell surface. On the basis of previous studies, we propose a new concept-“DSCs-derived IL-33 is involved in regulating the immune balance of Th1/Th2 and Th17/Treg through modulating DICs differentiation”. The present subject is undertaken to investigate the characters of IL-33/ST2 expression at maternal-fetal interface, and probe the biological effects (including proliferation, apoptosis, adhesion, invasion, differentiation and cytokine secretion) of IL-33 on DSCs, DICs and Tros. This subject will be helpful to reveal the mechanism of IL-33 in modulating Th1/Th2 and Th17/Treg immune balance at maternal-fetal interface in hopes of providing clinicians with a treatment strategy of unexplained recurrent spontaneous abortion, furthermore, providing scientific evidences why sST2 may serve as a reliable indicator for judging the prognosis of pregnancy.

早孕期母胎界面蜕膜基质细胞（DSCs）、蜕膜免疫细胞（DICs）和滋养细胞（Tros）交互“对话”，诱导DICs分化发育、建立Th1/Th2及Th17/Treg免疫平衡是成功妊娠的关键。解析其内在驱动机制是免疫耐受研究的热点与难点。IL-33具有多种免疫调节效应，其配体ST2表达于多种免疫细胞表面；结合前期研究，我们构想“DSCs来源的IL-33诱导DICs分化发育及其功能调控，是形成母胎免疫耐受的重要机制”。本项目拟通过体外和动物模型实验揭示母胎界面IL-33/ST2、外周血可溶性ST2（sST2）表达特征，借助RNA干扰等方法，解析IL-33调控DSCs/Tros/DISs（NK、MΦ、T细胞）分化、增殖、侵袭等生物学行为，形成母胎免疫耐受的分子机制，为反复自然流产等病理妊娠的临床治疗探寻新的分子靶点（IL-33）；为建立以sST2作为早孕监护、预测妊娠预后的生物学标志提供科学依据。

早孕期母胎界面蜕膜基质细胞（DSCs）、蜕膜免疫细胞（DICs）和滋养细胞（Tros）交互“对话”，诱导DICs分化发育、建立Th1/Th2及Th17/Treg免疫平衡是成功妊娠的关键。解析其内在驱动机制是免疫耐受研究的热点与难点。IL-33具有多种免疫调节效应，其配体ST2表达于多种免疫细胞表面；结合前期研究，我们构想“DSCs来源的IL-33诱导DICs分化发育及其功能调控，是形成母胎免疫耐受的重要机制”。本项目拟通过体外和动物模型实验揭示母胎界面IL-33/ST2、外周血可溶性ST2（sST2）表达特征，借助RNA干扰等方法，解析IL-33调控DSCs/Tros/DISs（NK、MΦ、T细胞）分化、增殖、侵袭等生物学行为，形成母胎免疫耐受的分子机制，为反复自然流产等病理妊娠的临床治疗探寻新的分子靶点（IL-33）；为建立以sST2作为早孕监护、预测妊娠预后的生物学标志提供科学依据。