Nat Commun:双阴性T细胞抑制非酒精性脂肪性肝炎的发生发展

2021-02-07 xiaozeng MedSci原创

非酒精性脂肪性肝病(NAFLD)是全球范围内最主要的肝病发病原因之一。非酒精性脂肪性肝炎(NASH)是NAFLD的渐进性形式,其可能发展为肝硬化和肝细胞癌,并增加肝脏和心血管系统相关疾病的发病和死亡风

非酒精性脂肪性肝病(NAFLD)是全球范围内最主要的肝病发病原因之一。非酒精性脂肪性肝炎(NASH)是NAFLD的渐进性形式,其可能发展为肝硬化和肝细胞癌,并增加肝脏和血管系统相关疾病的发病和死亡风险。尽管在过去10年中已有许多NASH相关的发病机制研究,但目前尚无批准的NASH治疗方法。

肝炎在从肝脂肪变性到NASH的发生发展中起着至关重要的作用。既往研究显示,先天性和适应性免疫细胞均参与NASH的发病中,且抑制炎症可以减轻肝脏的损害并防止NASH的发生发展。

继承性cDNT转移减轻肥胖诱导的胰岛素抵抗和高脂饮食诱导的脂肪性肝炎

在该研究中,研究人员发现,CD4+T细胞转化为双阴性T细胞(cDNT)的继承性转移作用可以保护小鼠模型免受高脂饮食诱导的肝脂肪蓄积、小叶炎症和局灶性坏死。

cDNT在NASH发生发展过程中的机制示意图

cDNT能够选择性的抑制肝浸润性的Th17细胞和促炎性的M1巨噬细胞。M2巨噬细胞分泌的IL-10可降低cDNT的存活率和功能,从而保护M2巨噬细胞免于cDNT介导的细胞裂解作用。NKG2A作为一种细胞抑制因子,其能够促进IL-10诱导的细胞凋亡作用并减弱cDNT的抑制作用。


总而言之,该研究结果揭示了cDNT在饮食诱发的肥胖、2型糖尿病和NASH中的有效的保护作用,该改善作用归因于对肝炎性细胞的抑制。这项研究也支持了利用这种基于自身免疫细胞的自身疗法来治疗NASH的概念和可行性。


原始出处:

Sun, G., Zhao, X., Li, M. et al. CD4 derived double negative T cells prevent the development and progression of nonalcoholic steatohepatitis. Nat Commun 12, 650 (28 January 2021).

 

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    2021-05-27 liuli5079
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    2022-01-03 liye789132251
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    2021-04-28 qjddjq
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