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氧化脂氧PAPC改变调节T细胞分化,并降低它们在小鼠动脉样硬化中的保护功能

Brenna D Appleton¹, Sydney A Palmer², Harrison P Smith²

¹Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN (B.D.A., A.S.M.).

Arteriosclerosis, thrombosis, and vascular biology

|September 7, 2023

概括

氧化脂,如oxPAPC,损害调节性T细胞 (Treg) 功能和分化. 这种功能障碍降低了它们在小鼠中预防动脉样硬化进展的能力.

科学领域:

免疫学免疫学免疫学
心血管研究研究心血管研究

背景情况:

调节性T细胞 (Tregs) 对于预防动脉样硬化至关重要,但在疾病期间会下降.
在动脉样硬化中Treg功能障碍背后的机制尚未完全理解.
在动脉样硬化斑块中常见的氧化脂可能会影响T细胞功能.

研究的目的:

研究氧化1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC) 对Treg分化和功能的影响.
为了确定oxPAPC是否在动脉样硬化背景下有助于Treg功能障碍.

主要方法:

CD4+ T 细胞分化成具有或没有oxPAPC的Tregs.
使用了流细胞计,散装RNA测序和体外共同培养试验.
通过将Tregs转移到超脂性Ldlr-/-小鼠中,评估了动脉样硬化进展.

主要成果:

OxPAPC降低了Treg活力,并诱导了幸存细胞中的Th1-类表型,其特征是T-bet和IFN-γ表达增加.
IFN-γ信号传递部分调解了这些由oxPAPC引起的变化.
用OxPAPC治疗的Tregs在体外显示抑制能力降低,并且未能在体内抑制动脉样硬化进展.

结论:

像oxPAPC这样的氧化脂对Treg分化和功能产生负面影响,部分是通过IFN-γ信号传递.
这导致Tregs.的动脉动脉保护功能丧失.
这些发现突显了氧化脂在Treg功能障碍和动脉样硬化进展中的作用.

关键词:

动脉样硬化动脉样硬化细胞死亡是细胞死亡.疾病的进展疾病的进展干扰子干扰子干扰子脂酸是一种脂酸.

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