针对巨细胞干性因子,以减轻呼吸道病毒感染后的疾病
Mohd Arish1,2, Arka Sen Chaudhuri1,2, Janli Tang1,2
1Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA.
在病毒感染后,TCF4是膜巨细胞 (AM) 干和肺部修复的关键转录因子. 恢复TCF4水平可以帮助治疗慢性肺部疾病,如长期COVID.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 肺部医学 肺部医学
背景情况:
- 组织寄居的膜巨细胞 (AMs) 具有用于肺部维护的干状性质.
- 控制AM自我更新的转录调节剂及其在后病毒性肺病中的作用尚不清楚.
研究的目的:
- 为了确定调节AM干和功能的关键转录因子.
- 研究TCF4在AM维持,病毒感染反应和肺部修复中的作用.
- 探索TCF4作为慢性肺部疾病的治疗点.
主要方法:
- 在小鼠模型中对TCF4进行基因操纵.
- 使用流感和SARS-CoV-2的感染模型.
- 对AM扩散,表型和基因表达的分析.
- 评估肺病理,纤维化和生理功能.
- 人类肺组织样本的分析.
主要成果:
- TCF4对于AM的成熟和干性至关重要,控制了增殖,并防止了炎症转移.
- 在病毒感染后,TCF4的损失会加剧肺部疾病,而其强制表达会促进恢复,并防止严重疾病.
- TCF4对抗炎症通路 (β-catenin) 并保持AMs中的氧化酸化.
- 病毒感染和衰老抑制TCF4,TCF4在COVID后纤维化肺部慢性减少.
- 在病毒清除后老年小鼠中的TCF4过度表达恢复了肺功能并减少了纤维化.
结论:
- TCF4是AM干度和再生能力的关键调节者.
- 下调TCF4有助于慢性肺病和病毒感染后纤维化.
- 准TCF4为长期COVID和其他慢性肺部疾病提供了一个有希望的治疗策略.
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