酒精来源的乙酸盐通过促进皮质素乙烯化促进T细胞功能,从而损害T细胞功能
Vugar Azizov1,2, Michel Hübner1,2, Michael Frech1,2
1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
iScience
|July 24, 2023
概括
酒精代谢通过增加皮质素乙化,阻碍细胞迁移和免疫反应,损害T细胞功能. 这一发现表明皮质素是自身免疫性疾病治疗的目标.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 酒精是一种广泛消费的物质,已知对肝脏,心脏和大脑等器官有有害影响.
- 酒精消费对免疫系统产生重大影响,尤其是T细胞功能.
- 酒精影响T细胞的精确分子机制尚未完全理解.
研究的目的:
- 研究酒精消费如何在分子水平上损害T细胞功能.
- 为了确定特定的蛋白质和途径参与酒精诱导的T细胞功能障碍.
- 探索潜在的治疗目标,以减轻酒精对免疫力的负面影响.
主要方法:
- 在饮酒后在淋巴体器官中酸盐积累的分析.
- 研究酸盐对T细胞中皮质素乙化的作用.
- 使用体外和体内模型,包括T细胞测定和小鼠流感感染模型.
- 采用诸如皮质素淘汰和突变皮质素表达等技术来评估功能影响.
主要成果:
- 酒精代谢物乙酸盐在淋巴体器官中积累,并增加T细胞中的皮质素乙烯化.
- 乙化皮质素显示了纤维状动因结合的减少,损害了T细胞迁移,免疫突触的形成和激活.
- 突变的抗乙化皮质素部分挽救了乙酸诱导的T细胞迁移缺陷.
- 乙诱导的细胞骨变化抑制了T细胞激活,增殖和免疫突触形成,在体外和体内.
结论:
- 酒精通过皮质素乙化损害T细胞功能,影响细胞骨动力学.
- 皮质素是酒精对T细胞免疫的有害影响的关键调解剂.
- 向皮质素乙化可能为治疗T细胞介导的自身免疫性疾病提供一种策略.
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