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双阴性T细胞通过Th9细胞分化调节肝纤维化的进展

Chenyang Han¹, Hongyan Pei², Yongjia Sheng¹

¹The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.

Liver international : official journal of the International Association for the Study of the Liver

|May 30, 2023

概括

双阴性T细胞 (DNTs) 通过通过TNF-α信号传递增强Th9细胞分化来促进肝纤维化. 用抗体阻止这种途径会减少Th9细胞的比例和纤维化进展.

科学领域:

免疫学免疫学免疫学
肝病学肝病学是一种肝病学.
细胞生物学细胞生物学

背景情况:

以前的研究将双阴性T细胞 (DNT) 与NLRP3激活和通过TNF-α的肝纤维化进展联系起来.
在肝纤维化中DNTs在调节Th9细胞分化中的特定作用仍然不清楚.

研究的目的:

研究DNTs在肝纤维化背景下调节Th9细胞分化的机制.
阐明参与DNT介导的Th9细胞促进的信号通路.

主要方法:

对肝纤维化患者的周围血液进行分析.
在体内研究使用肝纤维化的小鼠模型.
在体外同培实验中,使用原始T细胞进行了同培实验.
用IL-9和TNF-α单克隆抗体 (mAbs) 进行治疗.
对TNFR2-STAT5-NF-κB通路激活的评估.

主要成果:

在肝纤维化患者中观察到DNT和Th9细胞的比例增加,并且与积极相关.
在体内,DNTs促进了Th9细胞分化,并激活了TNFR2-STAT5-NF-κB通路.
IL-9和TNF-α mAbs抑制了DNT介导的作用,并减少了Th9细胞的比例.
在体外,DNTs促进了天真T细胞分化为Th9细胞,这一效应被TNF-α mAbs.

结论:

通过分泌TNF-α,DNTs促进肝纤维化进展,从而激活TNFR2-STAT5-NF-κB通路并驱动Th9细胞分化.
在肝纤维化的发病过程中,DNTs和Th9细胞之间存在显著的相互作用.
准DNT-Th9细胞轴,特别是TNF-α信号传递,代表了肝纤维化的潜在治疗策略.

关键词:

不同化的差异化差异化.双阴性T细胞是双阴性T细胞.辅助性T细胞9的第九种细胞.这是一种炎症炎症炎症炎症.肝脏纤维化肝脏纤维化瘤死亡因子-α

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