过酶增殖器激活受体α是由血管素转化酶诱导的巨细胞增强免疫功能的重要因素
Suguru Saito1, DuoYao Cao1, Ellen A Bernstein1
1Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Research square
|May 15, 2024
概括
增加血管酶转化酶 (ACE) 表达增强了巨细胞通过过氧酶增殖器激活受体α (PPARα) 的免疫功能. 这一途径增强了抗瘤和抗菌免疫力,对自然防御机制至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 骨髓状细胞中 ангиотензин转化酶 (ACE) 的上调自然增强免疫力.
- 过度表达ACE的小鼠 (ACE10/10) 显示出改善的抗瘤和抗菌反应,但机制尚不清楚.
研究的目的:
- 阐明ACE诱导的巨细胞功能上调背后的分子机制.
- 调查过氧酶增殖器激活受体α (PPARα) 在ACE介导免疫增强中的作用.
主要方法:
- 使用LysM-Cre系统生成了骨髓系选择性PPARα缺乏ACE10/10小鼠 (A10-PPARα-Cre).
- 在小鼠模型中评估了瘤生长,细胞因子产生,抗原呈现,CD8+T细胞活性和抗菌作用.
- 利用人类THP-1-ACE衍生的巨体和PPARα调节剂 (激动剂WY 14643,抗剂GW6471) 进行体外验证.
主要成果:
- 在过度表达ACE的巨细胞中,PPARα的表达被上调.
- 在A10-PPARα-Cre小鼠中,PPARα的减少导致瘤生长的增加和对MRSA的抗菌活性受损.
- 枯竭减少了巨细胞因子的产生,抗原的呈现,细胞和杀死细菌,从而削弱了CD8+ T细胞的反应.
- 人类THP-1-ACE巨体表现出增强的细胞毒性和杀死细菌,由PPARα激动剂进一步增强,并被对抗剂抑制.
结论:
- 过氧体增殖器激活受体α (PPARα) 是ACE依赖性巨细胞功能上调的关键调节者.
- PPARα在增强抗瘤免疫力和抗菌杀菌活性方面发挥着至关重要的作用.
- 准ACE-PPARα轴有可能调节癌症和传染病中的免疫反应.
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