在病毒感染期间,需要维持强烈的自然杀手细胞增殖所需的正规IRE1功能
Jessica Vetters1,2, Mary van Helden2,3,4, Clint De Nolf1,2,5,6
1Laboratory for ER Stress and Inflammation, VIB Center for Inflammation Research, Ghent, Belgium.
iScience
|January 1, 2024
概括
展开的蛋白质反应 (UPR) 途径,涉及IRE1/XBP1,对于病毒感染期间的自然杀手 (NK) 细胞增殖至关重要. 这种正规的UPR激活支持NK细胞在微生物挑战后扩张.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 展开的蛋白质反应 (UPR) 维持了内质网膜 (ER) 恒常性,主要是在分泌细胞中.
- 在免疫细胞中,UPR的非法典性作用正在出现.
- IRE1 (需要氨基酸酶1) 信号通路是UPR的一个关键分支.
研究的目的:
- 研究UPR的IRE1信号分支在自然杀手 (NK) 细胞中的功能.
- 评估IRE1/XBP1在NK细胞稳态和对病毒感染的反应中的作用.
主要方法:
- 对IRE1和XBP1.1的NK细胞内在缺陷的分析.
- 利用混合骨髓仿真体来研究NK细胞竞争.
- 使用CITE-Seq分析感染期间NK细胞的基因表达变化.
主要成果:
- IRE1/XBP1的缺陷没有影响基底NK细胞平衡或总体的病毒性MCMV感染结果.
- 在竞争环境中,IRE1充足的NK细胞在病毒感染后表现出增殖优势.
- CITE-Seq显示了早期的IRE1诱导和感染时的规范UPR签名激活.
结论:
- 在病毒感染早期,IRE1/XBP1激活对于强大的NK细胞增殖至关重要.
- IRE1/XBP1通路作为繁殖NK细胞中规范UPR反应的一部分.
- 这凸显了UPR在微生物挑战期间适应性免疫中发挥的关键作用.
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