International immunopharmacology · 2024
Immunomodulation in Endometriosis: Investigating the interrelationship between VISTA expression and Escherichia.Shigella-Associated metabolites.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chen Yichen, Che Xuan, Rong Yishen, Zhu Jue, Yu Yayuan, Xu Hong, Sun Yuhui, Chen Huan, Yan Lifeng, Chen Liang, Xu Yanan, Zhang Jing
Аннотация
AIMS: 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.
MAIN 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.
KEY FINDINGS: 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.
SIGNIFICANCE: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.
MAIN 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.
KEY FINDINGS: 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.
SIGNIFICANCE: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.