Abstract：
OBJECTIVE: Endometriosis is characterized by an abnormal immune microenvironment. Despite the extensive use of immune therapies, the application of immune checkpoint inhibitors in endometriosis lacks confidence due to the instability of preclinical research data. This study aims to elucidate the regulation of the immune inhibitory checkpoint VISTA and its effects on T cells from the perspective of microbiota and metabolism.
METHODS: We divided endometriosis patients into high and low groups based on the expression levels of VISTA in lesion tissues. We collected peritoneal fluid samples from these two groups and performed 16 s RNA sequencing and metabolomics analysis to investigate microbial diversity and differential metabolites. Through combined analysis, we identified microbial-associated metabolites and validated their correlation with VISTA and CD8 + T cells using ELISA and immunofluorescence. In vitro experiments were conducted to confirm the regulatory relationship among these factors.
RESULTS: Our findings revealed a distinct correlation between VISTA expression and the microbial colony Escherichia.Shigella. Moreover, we identified the metabolites LTD4-d5 and 2-n-Propylthiazolidine-4-carboxylic acid as being associated with both Escherichia.Shigella and VISTA expression. In vitro experiments confirmed the inhibitory effects of these metabolites on VISTA expression, while they demonstrated a positive regulation of CD8 + T cell infiltration into endometriotic lesions.
CONCLUSIONS: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.
METHODS: We divided endometriosis patients into high and low groups based on the expression levels of VISTA in lesion tissues. We collected peritoneal fluid samples from these two groups and performed 16 s RNA sequencing and metabolomics analysis to investigate microbial diversity and differential metabolites. Through combined analysis, we identified microbial-associated metabolites and validated their correlation with VISTA and CD8 + T cells using ELISA and immunofluorescence. In vitro experiments were conducted to confirm the regulatory relationship among these factors.
RESULTS: Our findings revealed a distinct correlation between VISTA expression and the microbial colony Escherichia.Shigella. Moreover, we identified the metabolites LTD4-d5 and 2-n-Propylthiazolidine-4-carboxylic acid as being associated with both Escherichia.Shigella and VISTA expression. In vitro experiments confirmed the inhibitory effects of these metabolites on VISTA expression, while they demonstrated a positive regulation of CD8 + T cell infiltration into endometriotic lesions.
CONCLUSIONS: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.
摘要：
目的：子宫内膜异位症的特征是免疫微环境异常。尽管广泛使用免疫疗法，由于临床前研究数据的不稳定性,免疫检查点抑制剂在子宫内膜异位症中的应用缺乏信心.本研究旨在从微生物群和代谢的角度阐明免疫抑制检查点VISTA的调控及其对T细胞的影响。
方法：我们根据病灶组织中VISTA的表达水平将子宫内膜异位症患者分为高和低两组。我们收集了这两组的腹膜液样本，并进行了16sRNA测序和代谢组学分析，以研究微生物多样性和差异代谢物。通过组合分析,我们鉴定了微生物相关代谢物,并使用ELISA和免疫荧光验证了它们与VISTA和CD8+T细胞的相关性.进行体外实验以确认这些因素之间的调节关系。
结果：我们的发现揭示了VISTA表达与埃希氏菌菌落之间的明显相关性。志贺氏菌.此外，我们确定了代谢物LTD4-d5和2-n-丙基噻唑烷-4-羧酸与两种埃希氏菌有关。志贺氏菌和VISTA表达。体外实验证实了这些代谢物对VISTA表达的抑制作用，同时他们表现出CD8+T细胞浸润到子宫内膜异位病变的正调控。
结论：这项研究揭示了微生物多样性之间的联系，代谢物，和VISTA在子宫内膜异位症免疫微环境中的表达，为治疗干预提供潜在的目标。
方法：我们根据病灶组织中VISTA的表达水平将子宫内膜异位症患者分为高和低两组。我们收集了这两组的腹膜液样本，并进行了16sRNA测序和代谢组学分析，以研究微生物多样性和差异代谢物。通过组合分析,我们鉴定了微生物相关代谢物,并使用ELISA和免疫荧光验证了它们与VISTA和CD8+T细胞的相关性.进行体外实验以确认这些因素之间的调节关系。
结果：我们的发现揭示了VISTA表达与埃希氏菌菌落之间的明显相关性。志贺氏菌.此外，我们确定了代谢物LTD4-d5和2-n-丙基噻唑烷-4-羧酸与两种埃希氏菌有关。志贺氏菌和VISTA表达。体外实验证实了这些代谢物对VISTA表达的抑制作用，同时他们表现出CD8+T细胞浸润到子宫内膜异位病变的正调控。
结论：这项研究揭示了微生物多样性之间的联系，代谢物，和VISTA在子宫内膜异位症免疫微环境中的表达，为治疗干预提供潜在的目标。
