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抑制LTβR信号激活了肺中的WNT诱导的再生
Thomas M Conlon1, Gerrit John-Schuster1, Danijela Heide2
1Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Neuherberg, Germany.
Nature
|November 5, 2020
概括
向淋巴毒素β受体 (LTβR) 信号可以治疗慢性肺炎和损伤. 在COPD模型中,阻断LTβR抑制了三级淋巴细胞结构,防止细胞死亡,并促进肺组织再生.
科学领域:
- 免疫学
- 肺病学
- 细胞生物学
背景情况:
- 淋巴毒素β受体 (LTβR) 信号驱动淋巴细胞新生和三级淋巴细胞结构,与慢性炎症相关.
- LTβR在肺损伤中的作用,其调节机制以及慢性阻塞性肺病 (COPD) 的治疗潜力尚不清楚.
研究的目的:
- 在吸烟相关的肺部疾病中研究LTβR信号.
- 阐明LTβR驱动的肺病理背后的机制.
- 在COPD模型中评估LTβR阻断的治疗效果.
主要方法:
- 从COPD患者和暴露在香烟烟雾中的小鼠肺组织中分析LTβR连接体表达和信号通路.
- 在上皮细胞中评估非正规的NF-κB和TGFβ信号.
- 在小鼠模型中评估LTβR阻塞对三级淋巴细胞结构,肺再生,纤维化和肌肉衰竭的影响.
主要成果:
- 在吸烟相关的COPD肺部中观察到增加的LTβR连接物,非正规的NF- kB信号传递和LTβR基因表达.
- 在小鼠中,LTβR阻塞破坏了可诱导的支气管相关的淋巴组织,促进了肺部再生,并逆转了气道纤维化和肌肉衰竭.
- 在机理上,LTβR阻断降低了表皮NF- kB激活,TGFβ信号传递和细胞亡,同时激活了膜前细胞中的WNT/ β- 素信号传递.
结论:
- 在慢性肺炎中,LTβR信号对慢性肺炎和组织损伤有重要作用.
- 治疗性抑制LTβR信号提供了治疗COPD的有希望的策略.
- LTβR阻塞结合了抗炎作用和组织再生特性来修复肺部.
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