化基碳化合物受体抑制剂抑制了自免疫性肝炎中Th17细胞免疫力
Li Gao1, Wei Zhang1, Lina Zhang2
1Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
Journal of autoimmunity
|December 24, 2023
概括
在自身免疫性肝炎 (AIH) 中阻断基碳化合物受体抑制剂 (AHRR) 恢复T-辅助17 (Th17) 细胞功能,并减少肝损伤. 这种方法可以通过调节免疫反应来为AIH提供一种新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 肝病学 肝病学是一种肝病学.
- 分子生物学分子生物学
背景情况:
- 辅助T17 (Th17) 细胞在自身免疫性肝炎 (AIH) 病原发生过程中至关重要.
- 在AIH中失调的Th17细胞对基碳化合物受体 (AhR) 激活的反应不佳.
- 基碳化合物受体抑制剂 (AHRR) 抑制了AhR活性,其调节可能在AIH中异常.
研究的目的:
- 调查AIH中对AhR的缺陷Th17细胞反应是否源于异常的AHRR调节.
- 在AIH的小鼠模型中评估阻断AHRR的治疗潜力.
主要方法:
- 将AIH患者和健康对照的Th17细胞进行比较,评估对具有和没有AHRR沉默的AhR配体的反应.
- 在人性化小鼠中利用康卡纳瓦林-A (Con-A) 诱导的肝损伤模型来测试AHRR阻塞疗法.
- 给药的2'-deoxy-2'-fluoro-d-arabinonucleic acid (FANA) 寡核酸可以在体内静止AHRR.
主要成果:
- 在暴露于AhR配体l-kynurenine时,AIH Th17细胞的AHRR被上调.
- 在AIH患者的Th17细胞中,AHRR沉默增强了对l-kynurenine的反应,增加了CYP1A1并降低了IL17A.
- 在小鼠体内,AHRR阻塞减少了肝损伤标志物,炎症,并增加了调节性免疫细胞.
结论:
- 阻断AHRR恢复Th17细胞对AIH中的AhR的反应,并通过尿素生成限制Th17细胞的分化.
- 在体内,AHRR静音减轻了人性化的小鼠模型中的肝损伤,这表明了治疗潜力.
- AHRR封锁成为调节效应因子Th17免疫力和恢复AIH中的免疫平衡的一个有希望的策略.
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