IL-17将瘤抑制剂LKB1与胃肠道炎症和多重症联系在一起
Shelby E Compton1, Lisa M DeCamp1, Brandon M Oswald1
1Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.
瘤抑制剂肝激酶B1 (LKB1) 中的突变通过促进IL-17产生T细胞来驱动胃肠道聚的生长. 向CRTC2-IL-17通路在小鼠模型中抑制了多胞体的发展.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 瘤抑制剂肝激酶B1 (LKB1) 的突变与胃肠道 (GI) 息肉的发展有关.
- 驱动LKB1缺陷GI息肉生长的精确机制在很大程度上是未知的.
研究的目的:
- 为了确定LKB1依赖的GI聚生长的新型驱动因素.
- 阐明将LKB1损失与多体形成联系起来的分子机制.
- 探索针对已识别的途径的治疗策略.
主要方法:
- 来自异性LKB1突变的小鼠的肠道肠道瘤的分析 (Stk11).
- 在LKB1缺陷模型中T细胞分化的体外和体外研究.
- 关于CREB监管的转录协活性剂2 (CRTC2) 信号的研究.
- 在Peutz-Jeghers综合征的小鼠模型中,CRTC2删除和IL-17阻断.
主要成果:
- 这种LKB1脱素不足促进了致病性IL-17产生T辅助17 (TH17) 和T细胞毒性17 (Tc17) 细胞的分化.
- 异常的CRTC2-依赖信号传递介导病原性TH17细胞程序下游的LKB1损失.
- 通过CRTC2删除或IL-17阻断准CRTC2-IL-17轴,在小鼠模型中降低了GI息肉的生长.
结论:
- LKB1充当依赖IL-17的炎症T细胞反应的关键调节者或守门人.
- 一个新的CRTC2-IL-17信号轴被确定为LKB1突变肠道瘤生长的驱动因素.
- 这一途径为LKB1-突变性胃肠道瘤提供了潜在的治疗标.
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