福克索1驱动了Th17细胞命运的TGFβ1依赖二分法
Mengjuan Zhang1, Yude Guan1, Meijuan Han1
1College of Life Sciences, Research Institute of Transplant Medicine, Tianjin First Central Hospital, Nankai University, No. 94 Weijin Road, Tianjin 300071, China.
Journal of leukocyte biology
|January 9, 2024
概括
转录因子Foxo1调节T助手17细胞分化,区分致病性和非致病性类型. 较低的Foxo1水平与自身免疫性疾病的严重程度相关,这表明Foxo1是治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 这是一种自身免疫力.
背景情况:
- 辅助T17 (Th17) 细胞在免疫和自身免疫中具有双重作用.
- 转化生长因子β1 (TGF-β1) 促进非病原性Th17分化,而TGF-β3和活性素驱动病原性Th17表型.
- 控制Th17细胞致病性的分子机制尚不清楚.
研究的目的:
- 研究转录因子Foxo1在调节致病性与非致病性T助手17细胞分化中的作用.
- 探索Foxo1作为自身免疫性疾病治疗点的潜力.
主要方法:
- 对患有紫外线炎的患者的Foxo1表达的分析以及对实验性自身免疫性紫外线炎小鼠模型的分析.
- 在病原性条件下研究Foxo1表达对Th17细胞分化的影响.
- 检查TGF-β1信号传递,Foxo1和脂肪酸代谢之间的联系.
- 药物查以确定可调节Foxo1.1的化合物.
主要成果:
- 福克索1表达以TGF-β1剂量依赖的方式上调调节,并关键调节致病性Th17细胞命运.
- 降低Foxo1水平与膜炎患者和模型的疾病严重程度增加相关.
- 宫外 Foxo1 表达抑制了致病的 Th17A 生产.
- TGF-β1诱导的Foxo1增强脂肪酸代谢途径,支持非致病的Th17分化.
- 确定了几种FDA批准的药物,可以调节Foxo1.1.
结论:
- 福克索1作为一个分子开关,以TGF-β1依赖的方式控制致病与非致病的Th17分化.
- 向Foxo1代表了对自身免疫性疾病的潜在治疗策略.
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