腹腔大巨噬细胞和小巨噬细胞在子宫内膜异位症发病中的分子机制研究

Endometriosis, keeping high morbidity, affects the patients both physically and psychologically. But its pathogenesis is still unclear. Peritoneal macrophage is professional phagocyte and antigen-presenting cell and plays a major role in the pathogenesis of endometriosis. Dysfunctions of peritoneal macrophages are discovered in numerous clinical studies. Moreover, the functional change of peritoneal macrophages affects the development of endometriosis in an animal model. However, because of the ignorance of heterogeneity of macrophage subtypes and incomplete functional assessment, the exact function and impact of macrophage in endometriosis remains unclear. Depending on the recent researches, peritoneal macrophages consist of large peritoneal macrophage (LPM) and small peritoneal macrophage (SPM), which keep different ontogeny and properties. In our previous study, we have found that LPM and SPM play different roles in EMs by transforming into M1 and M2 respectively. We will use high-throughput single-cell transcription sequencing analysis and cytokines detection analysis, combined with in vitro cell co-culture experiments and novel animal model to identify and verify the key pathways and cytokines in EMs. To explore new methods for the treatment of EMs, we will neutralize key cytokines by efficient antibodies, block key signaling pathways by small-molecule inhibitor and remodel macrophage in vitro.

子宫内膜异位症（EMs）发病率高，严重影响妇女身心健康，但发病机制尚不明确。腹腔巨噬细胞具备细胞吞噬和抗原递呈两大作用，在EMs病程中扮演重要角色。临床研究证明腹腔巨噬细胞在EMs中功能异常，动物实验提示巨噬细胞功能状态影响EMs病程进展。但在既往研究中忽略了巨噬细胞的异质性且未完善评估其功能，导致巨噬细胞在EMs中的功能状态和作用尚不明确。最新研究表明腹腔巨噬细胞由起源和功能不同的腹腔大巨噬细胞（LPM）和腹腔小巨噬细胞（SPM）组成，我们的前期工作表明，两者在EMs发病中扮演不同的角色，LPM向M1转化，而SPM向M2转化。我们将采用单细胞转录组测序和悬液芯片技术，结合细胞共培养实验和新型EMs动物模型，筛选并验证两种巨噬细胞参与EMs病程进展的关键信号通路和细胞因子，并通过高效抗体中和靶点细胞因子、特异性阻断关键信号通路和巨噬细胞体外修饰重塑后回输等方法，探索治疗EMs的新方法。

子宫内膜异位症（EM）发病率高，严重影响妇女身心健康，但发病机制尚不明确。腹腔巨噬细胞具备细胞吞噬和抗原递呈两大作用，在EM病程中扮演重要角色。临床研究证明腹腔巨噬细胞在EM中功能异常，动物实验提示巨噬细胞功能状态影响EM病程进展。但在既往研究中忽略了巨噬细胞的异质性且未完善评估其功能，导致巨噬细胞在EM中的功能状态和作用尚不明确。最新研究表明腹腔巨噬细胞由起源和功能不同的腹腔大巨噬细胞（LPM）和腹腔小巨噬细胞（SPM）组成，我们的前期工作表明，两者在EM发病中扮演不同的角色，LPM向M1转化，而SPM向M2转化。我们将采用单细胞转录组测序和悬液芯片技术，结合细胞共培养实验和新型EM动物模型，筛选并验证两种巨噬细胞参与EM病程进展的关键信号通路和细胞因子，并通过高效抗体中和靶点细胞因子、特异性阻断关键信号通路和巨噬细胞体外修饰重塑后回输等方法，探索治疗EM的新方法。