对衰老敏感的昼夜节律控制着皮肤抗病毒免疫力
Stephen J Kirchner1,2, Vivian Lei1, Paul T Kim1
1Department of Dermatology.
JCI insight
|September 19, 2023
概括
老化的皮肤老化.
科学领域:
- 免疫学 免疫学 免疫学
- 皮肤病学 皮肤病学
- 时间生物学 时间生物学
背景情况:
- 老化皮肤表现出对病毒感染的敏感性增加.
- 这种与免疫发生相关的免疫风险的潜在机制尚未完全理解.
研究的目的:
- 研究昼夜调节器和抗病毒蛋白 (AVP) 在老年皮肤免疫反应中的作用.
- 探索昼夜恢复作为一个潜在的抗病毒策略,老龄化人口.
主要方法:
- 在老鼠和人类皮肤中评估了AVP和昼夜调节器 (Bmal1,时钟) 的水平.
- 研究了Bmal1和Clock对节律性AVP表达的控制.
- 研究了IL-27信号干扰和基因删除/阻断对昼夜AVP调节的影响.
- 在皮肤模型中评估了对简单疹病毒1感染的昼夜增强剂 (nobiletin,SR8278) 的疗效.
主要成果:
- 老化皮肤显示AVP和昼夜调节器Bmal1和Clock的水平降低.
- Bmal1和Clock调节节律性AVP表达,这种过程因IL-27信号干扰和Bmal1/Clock基因改变而受损.
- 循环节增强疗法有效地减少了皮肤扩张和角质细胞中的病毒感染,以BMAL1/CLOCK依赖的方式.
- 这些疗法逆转了老年皮肤和角质细胞对病毒感染的敏感性.
结论:
- 皮肤抗病毒免疫受一种进化保守的,对年龄敏感的昼夜机制调节.
- 恢复昼夜功能是对抗老年人感染的有希望的抗病毒策略.
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