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失调的抗氧化剂信号传递和受损的线粒体完整性会对肝脏疾病中的调节性T细胞功能和活力产生负面影响

Trishan Vaikunthanathan¹, Emmanuelle Landmann¹, Diana Marin Correa¹

¹Department of Inflammation Biology, Institute of Liver Studies, School of Immunology and Microbial Sciences, James Black Centre, King's College London, London, SE5 9NU, United Kingdom.

|September 1, 2023

概括

来自肝硬化患者的调节性T细胞 (Tregs) 由于氧化应激而表现出功能受损. 增强Treg抗氧化途径可能为晚期肝病提供新疗法.

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.
氧化压力研究研究氧化压力研究

背景情况:

慢性炎症性疾病,如肝硬化 (LC) 涉及失调的炎症和氧化应激.
调节性T细胞 (Tregs) 对免疫平衡至关重要,但它们对氧化应激的反应尚未完全理解.

研究的目的:

研究氧化应激对Treg功能,稳定性和肝硬化生存的影响.
探索Nrf2/HO-1抗氧化途径在LC中的Treg功能障碍中的作用.

主要方法:

从LC患者和健康对照 (HC) 的Tregs进行比较.
评估Treg氧化还原状态,包括ROS,Nox2活性,线粒体功能和Nrf2信号.
利用小鼠模型和CRISPR/Cas9来研究Nrf2和HO-1在Treg功能中的相关性.

主要成果:

LC Tregs表现出抑制功能的降低,表型异常和亡的增加,与疾病严重程度相关.
失调的Nrf2信号导致了较低的HO-1,增加的Nox2活性,以及LC Tregs中的线粒体功能受损.
患者血清中的培养控制Tregs部分模仿了功能缺陷.

结论:

功能性氧化还原稳定对于Treg功能,稳定性和生存至关重要.
针对Treg特异性抗氧化路径,为与氧化损伤相关的疾病 (如晚期肝病) 提供了潜在的治疗策略.

关键词:

肝硬化是肝硬化的一种疾病.线粒体中的线粒体.Nrf2 / 血氧化酶-1 的作用.氧化应激是一种氧化应激.氧化还原平衡 (redox homeostasis) 是一种监管性T细胞是什么意思

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