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Persistent deficiency of mucosa-associated invariant T (MAIT) cells during alcohol-related liver disease
Cell and Bioscience ( IF 6.1 ) Pub Date : 2021-07-28 , DOI: 10.1186/s13578-021-00664-8
Yujue Zhang 1 , Yuanyuan Fan 2 , Wei He 3 , Yi Han 4 , Huarui Bao 5 , Renjun Yang 1 , Bingbing Wang 1 , Derun Kong 1, 4 , Hua Wang 2, 6
Affiliation  

Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Inflammatory response is a basic pathological feature of ALD. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the changes of MAIT cell in ALD remains unclear. In this study, the levels of MAIT cell were significantly decreased in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction of circulating MAIT cells was correlated with liver function in patients with cirrhosis. Functional changes among circulating MAIT cells in patients with alcoholic cirrhosis, including increased production of IL-17A and perforin, and reduced production of TNF-α. Plasma cytokine and chemokine levels were quantified using multiple immunoassays and ELISA. Serum levels of chemokine IL-8 were correlated with MAIT cell frequency in patients with alcoholic cirrhosis. Moreover, no differences were observed in the expression of CCR6, CXCR6, and PD-1 in circulating MAIT cells of patients with alcoholic cirrhosis. The MAIT cells in patients with alcoholic cirrhosis were prone to apoptosis, which was promoted by IL-12, IL-18, and IL-8. Our findings indicate persistent MAIT cell loss during alcohol-related liver disease and suggest that MAIT cells can be promising indicator and therapeutic targets in ALD.

中文翻译:

酒精相关性肝病期间黏膜相关不变性 T (MAIT) 细胞持续缺乏

酒精相关性肝病 (ALD) 是慢性肝病的主要原因。炎症反应是 ALD 的基本病理特征。黏膜相关不变 T(MAIT) 细胞是先天免疫细胞的新群体,可能在各种炎症性疾病中被耗尽。然而,ALD中MAIT细胞的变化尚不清楚。本研究中,酒精性脂肪肝、酒精性肝硬化和混合性肝硬化(酒精+病毒)患者的MAIT细胞水平显着降低。此外,循环 MAIT 细胞的减少与肝硬化患者的肝功能相关。酒精性肝硬化患者循环 MAIT 细胞的功能变化,包括 IL-17A 和穿孔素的产生增加,以及 TNF-α 的产生减少。血浆细胞因子和趋化因子水平使用多重免疫测定和 ELISA 进行量化。血清趋化因子 IL-8 水平与酒精性肝硬化患者的 MAIT 细胞频率相关。此外,酒精性肝硬化患者循环 MAIT 细胞中 CCR6、CXCR6 和 PD-1 的表达未观察到差异。酒精性肝硬化患者的 MAIT 细胞易发生凋亡,这是由 IL-12、IL-18 和 IL-8 促进的。我们的研究结果表明,酒精相关性肝病期间 MAIT 细胞持续丢失,并表明 MAIT 细胞可以成为 ALD 的有希望的指标和治疗靶点。酒精性肝硬化患者循环 MAIT 细胞中 CCR6、CXCR6 和 PD-1 的表达未观察到差异。酒精性肝硬化患者的 MAIT 细胞易发生凋亡,这是由 IL-12、IL-18 和 IL-8 促进的。我们的研究结果表明,酒精相关肝病期间 MAIT 细胞持续丢失,并表明 MAIT 细胞可以成为 ALD 的有希望的指标和治疗靶点。酒精性肝硬化患者循环 MAIT 细胞中 CCR6、CXCR6 和 PD-1 的表达未观察到差异。酒精性肝硬化患者的 MAIT 细胞易发生凋亡,这是由 IL-12、IL-18 和 IL-8 促进的。我们的研究结果表明,酒精相关性肝病期间 MAIT 细胞持续丢失,并表明 MAIT 细胞可以成为 ALD 的有希望的指标和治疗靶点。
更新日期:2021-07-29
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