NMP4 regulates the innate immune response to influenza A virus infection.
NMP4 regulates the innate immune response to influenza A virus infection.
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NMP4 调节对甲型流感病毒感染的先天免疫反应。
DOI：
10.1038/s41385-020-0280-z
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发表时间：
2021
影响因子：
8
通讯作者：
Zhou,Baohua
中科院分区：
文献类型：
--
作者：
Yang,Shuangshuang;Adaway,Michele;Du,Jianguang;Huang,Shengping;Sun,Jie;Bidwell,JosephP;Zhou,Baohua
严重的甲型流感病毒感染通常会引发过度和有害的肺部炎症，伴有大量细胞浸润和细胞因子和趋化因子的过量产生。我们发现了核基质蛋白4 （NMP4）的新功能，NMP4是一种含锌指的转录因子，在骨形成和精子发生中起作用，在调节抗病毒免疫反应和免疫病理中起作用。缺乏nmp4的小鼠不受H1N1流感感染，体重仅减轻5%，而野生型小鼠体重减轻20%。虽然对病毒清除、CD8/CD4 T细胞或体液反应没有影响，但肺结构细胞或造血细胞缺乏nmp4会显著减少单核细胞和中性粒细胞向肺的募集。与气道内先天细胞减少一致，流感感染的nmp4缺陷小鼠的趋化因子基因ccl2、ccl7和cxcl1以及促炎细胞因子基因il1bandil6的表达显著降低。此外，NMP4结合趋化因子基因的启动子和/或保守的非编码序列，并调节其在小鼠肺上皮细胞和巨噬细胞中的表达。我们的数据表明，NMP4在甲型流感感染时促进单核细胞和中性粒细胞吸引趋化因子的表达，导致先天性炎症和肺组织损伤的加剧。
Severe influenza A virus infection typically triggers excessive and detrimental lung inflammation with massive cell infiltration and hyper-production of cytokines and chemokines. We identified a novel function for nuclear matrix protein 4 (NMP4), a zinc-finger-containing transcription factor playing roles in bone formation and spermatogenesis, in regulating antiviral immune response and immunopathology.Nmp4-deficient mice are protected from H1N1 influenza infection, losing only 5% body weight compared to a 20% weight loss in wild type mice. While having no effects on viral clearance or CD8/CD4 T cell or humoral responses, deficiency ofNmp4in either lung structural cells or hematopoietic cells significantly reduces the recruitment of monocytes and neutrophils to the lungs. Consistent with fewer innate cells in the airways, influenza-infectedNmp4-deficient mice have significantly decreased expression of chemokine genesCcl2,Ccl7andCxcl1as well as pro-inflammatory cytokine genesIl1bandIl6. Furthermore, NMP4 binds to the promoters and/or conserved non-coding sequences of the chemokine genes and regulates their expression in mouse lung epithelial cells and macrophages. Our data suggest that NMP4 functions to promote monocyte- and neutrophil-attracting chemokine expression upon influenza A infection, resulting in exaggerated innate inflammation and lung tissue damage.