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在结性脊柱炎中,PCSK9通过激活核因子-κB通路来促进T助手1和T助手17细胞的分化
Jianfei Cai1, Yinghui Jiang2, Fucai Chen3
1Department of Rheumatology and Immunology, Huadong Hospital Affiliated with Fudan University, Shanghai, China.
Immunity, inflammation and disease
|May 30, 2023
概括
蛋白转化酶亚素/素9型 (PCSK9) 通过NF-κB通路增加T助手1和T助手17细胞在结性脊髓炎 (AS) 中的分化. 这项研究澄清了PCSK9在AS发病过程中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 类风湿病学 类风湿病学
- 分子生物学分子生物学
背景情况:
- 之前的研究将プロ蛋白转化酶亚提利辛/凯类型9 (PCSK9) 与炎症和结性脊髓炎 (AS) 中的T辅助细胞 (Th) -17联系起来.
- 了解PCSK9在Th细胞分化中的确切作用对于AS的发病过程至关重要.
研究的目的:
- 研究PCSK9对AS患者T辅助细胞分化的影响.
- 阐明PCSK9对AS的Th细胞分化影响的分子机制.
主要方法:
- 在AS患者和健康对照者 (HCs) 中测量了血清PCSK9水平.
- 来自AS患者的原始CD4+T细胞被操纵用于PCSK9过度表达或淘汰.
- 细胞进行了极化测试,其中一些细胞接受了PMA (NF-κB激活剂) 的治疗.
- 分析了关键的蛋白质和细胞因子水平 (IFN-γ,IL-17A,IL-4,NF-κB,ERK,JNK).
主要成果:
- 与HC相比,AS患者的血清PCSK9水平较高.
- 过度表达PCSK9促进了Th1和Th17细胞的分化,增加了IFN-γ和IL-17A的产生.
- PCSK9调节的NF-κB信号传递,对p-NF-κB进行上调 p65.
- PMA治疗增强了Th1/Th17分化,并部分逆转了PCSK9对NF-κB和Th细胞分化的淘汰效应.
结论:
- 在AS中,PCSK9显著增强了Th1和Th17细胞分化.
- 这种效应通过一种依赖NF-κB的途径进行介导.
- 需要进一步验证才能完全确定PCSK9在AS中的作用.
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