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血清粉样蛋白A在肝脏中的表达促进了通过NFAT5激活突巨细胞和慢性关节炎

Meiling Li^1,2,3, Yu-Mi Kim^1,2, Jung Hee Koh⁴

¹Center for Integrative Rheumatoid Transcriptomics and Dynamics.

The Journal of clinical investigation

|March 1, 2024

概括

血清粉样蛋白A (SAA) 通过TLR2/4信号,激活激活T细胞5 (NFAT5) 的核因子,驱动巨细胞活动和关节炎. 这个肝关节轴突出显示SAA.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
类风湿病学类风湿病学

背景情况:

激活T细胞的核因子5 (NFAT5) 是一种度敏感的转录因子,由感染等刺激激活.
在损伤相关分子模式 (DAMP) 引发的炎症和免疫中NFAT5的作用尚未完全理解.

研究的目的:

研究NFAT5在DAMP触发的炎症和免疫中的作用.
阐明SAA-TLR2/4-NFAT5信号轴在巨细胞激活和关节炎中的作用.

主要方法:

用DAMP治疗巨细胞,并测量NFAT5的表达和活性.
在体外研究中评估了巨细胞迁移和化学反应.
在体内研究中使用了关节炎的小鼠模型,其中有NFAT5,TLR2 / 4或SAA的遗传废除或枯竭.
在肝脏中诱导SAA过度表达以评估其对关节损伤的影响.

主要成果:

几种DAMP增加了巨细胞中的NFAT5表达.
血清粉样蛋白A (SAA) 通过TLR2/4-JNK通路显著上调NFAT5的表达和活性.
SAA-TLR2/4-NFAT5轴以依赖IL-6和CCL2的方式促进了巨细胞迁移和化学反应.
在小鼠中,静脉内SAA注射加速了巨细胞透和关节炎进展.
对NFAT5或TLR2/4的遗传切除,以及针对骨髓细胞的NFAT5枯竭,挽救了SAA诱导的病理.
炎症性关节炎诱导了SAA在肝脏中的过度表达,而肝脏特异性的SAA过度表达加速了关节损伤.

结论:

SAA-TLR2/4-NFAT5轴对先天免疫和巨细胞激活至关重要.
SAA调解肝脏和关节之间的相互作用,加剧慢性关节炎.
针对SAA-TLR2/4-NFAT5通路可能为炎症性关节炎提供治疗策略.

关键词:

关节炎是一种关节炎.自身免疫性疾病是一种自身免疫性疾病.这是一种自身免疫力.炎症炎症是一种炎症.类风湿病学类风湿病学

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