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逆元件Lx9抑制了对病毒感染的免疫反应

Nenad Bartonicek^1,2, Romain Rouet^1,3, Joanna Warren¹

¹The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.

|August 10, 2022

概括

像Lx9c11这样的可转移元素调节免疫系统. 在小鼠中删除这种元素会对病毒感染造成致命的免疫过度反应, 这凸显了它在宿主生存中的作用.

科学领域:

基因组学
免疫学
分子生物学

背景情况:

可转移元素 (TE) 是移动DNA序列,包括哺乳动物基因组的很大一部分.
在TEs中的调节性DNA元素表明它在控制基因表达和细胞表型方面发挥作用.
古代保存的TE更有可能具有调节功能,但需要实验验证.

研究的目的:

研究一种特定的可移植元素Lx9c11在哺乳动物免疫反应中的调节作用.
确定删除Lx9c11在病毒感染期间对宿主生存的功能后果.

主要方法:

在小鼠中使用CRISPR- Cas9基因编辑来删除Lx9c11逆转移子.
用病毒感染小鼠以评估免疫反应和存活率.
分析了非编码RNA (Lx9c11-RegoS) 的表达及其对Schlafen家族基因的调节.

主要成果:

删除Lx9c11导致病毒感染的过度和致命的免疫反应.
Lx9c11对于产生Lx9c11-RegoS,一种非编码RNA至关重要.
Lx9c11-RegoS调节了Schlafen家族基因,减轻了Lx9c11淘汰小鼠的炎症并防止了死亡.

结论:

可转移的元素可以作为免疫系统的关键调节剂.
逆转录素Lx9c11及其衍生非编码RNA (Lx9c11- RegoS) 在病毒感染期间对宿主生存至关重要.
这些发现证明了可移植元素在控制免疫反应的作用,有利于宿主生存.

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