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Th9中的正反循环PU.1-IL9促进了类风湿性关节炎的发展

Jiajie Tu¹, Weile Chen¹, Wei Huang²

¹Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui, China.

Annals of the rheumatic diseases

|August 20, 2024

概括

在PU.1-IL-9轴驱动类风湿性关节炎 (RA) 病原体通过一个积极的反循环,涉及T助手9 (Th9) 细胞. 针对这一轴,为RA提供了一个有前途的治疗策略.

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:

辅助性T9 (Th9) 细胞,以PU.1和互白素-9 (IL-9) 生产为特征,与自身免疫性疾病有关.
PU.1-IL-9轴在类风湿性关节炎 (RA) 发病过程中的特定作用需要进一步阐明.

研究的目的:

为了研究PU.1,IL-9和RA病原体之间的关系.
探索针对RA中的PU.1-IL-9轴的治疗潜力.

主要方法:

在使用ELISA,西式涂抹和免疫组织化学的RA患者中量化PU.1和IL-9水平.
在关节炎模型 (CAIA,CIA) 中利用了淘汰赛小鼠模型 (PU.1,IL-9,IL-9R) 和治疗干预措施 (PU.1 抑制剂,IL-9 阻断抗体).
使用siRNAs和复合IL-9进行了体外研究,并进行了机械学研究 (露西法酶报告员,西部斑点,Chip-qPCR).

主要成果:

在RA患者中IL-9表达升高与临床疾病标志物呈正相关性.
向PU.1和IL-9在原抗体诱导性关节炎 (CAIA) 和原诱导性关节炎 (CIA) 模型中显著降低了炎症.
实验室研究证实IL-9的促炎作用,特别是在激活巨细胞和纤维细胞样同胞细胞,揭示了一个正反循环,PU.1通过IL-9R-JAK1/STAT3通路激活IL-9转录,IL-9通过IL-9R-JAK1/STAT3通路诱导PU.1.

结论:

PU.1-IL-9轴形成一个关键的正反循环,有助于RA的Th9细胞失调.
针对PU.1-IL-9信号轴代表了管理类风湿性关节炎的潜在治疗策略.

关键词:

关节炎,类风湿性关节炎细胞因子 (cytokines) 是一种细胞因子.的T-淋巴细胞.

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