迪戈辛及其衍生物通过对抗RORγt活动来抑制TH17细胞分化
Jun R Huh1, Monica W L Leung, Pengxiang Huang
1Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
Nature
|March 29, 2011
概括
迪戈辛抑制RORγt蛋白,这对T(H) 17细胞分化和自身免疫性疾病至关重要. 合成衍生品对开发针对克罗恩病和类风湿性关节炎等炎症性疾病的新疗法充满希望.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 药理学 药理学 是一个学科.
背景情况:
- 在自身免疫性疾病中,T(H) 17细胞起着关键作用.
- RORγt对于T(H) 17细胞的分化和功能至关重要.
- 这种T(H) 17通路是自身免疫性疾病的潜在治疗点.
研究的目的:
- 为了识别抑制RORγt转录活性的小分子.
- 在自身免疫性疾病模型中评估RORγt抑制剂的治疗潜力.
- 探索RORγt在人类T(H) 17细胞功能中的作用.
主要方法:
- 使用基于昆虫细胞的记者系统进行化学选.
- 对RORγt转录活性进行抑制测定.
- 在体外和体内对T(H) 17细胞分化的评估.
- 在自免疫性疾病的小鼠模型中评估治疗疗效.
主要成果:
- 迪戈辛被确定为RORγt的特定抑制剂.
- 迪戈辛抑制了小鼠T(H) 17细胞分化,并降低了自身免疫性疾病的严重程度.
- 非有毒的狄戈辛衍生物抑制了人类T (H) 17细胞中的IL-17诱导.
- 证实RORγt对于人类和小鼠的T细胞IL-17表达是必不可少的.
结论:
- 迪戈辛及其衍生物是有效的RORγt抑制剂.
- 准RORγt为治疗自身免疫性疾病提供了一个有希望的策略.
- 合成的迪戈辛衍生物可以作为新型抗炎疗法的模板.
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