A humanized mouse model to study NK cell biology during HIV infection.
A humanized mouse model to study NK cell biology during HIV infection.
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DOI：
10.1172/jci165620
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发表时间：
2022-12-15
影响因子：
15.9
通讯作者：
Zack, Jerome A.
中科院分区：
文献类型：
--
作者：
Kim, Jocelyn T.;Zack, Jerome A.
NK 细胞是具有抗病毒活性的先天免疫效应子的重要子集。然而，由于传统人源化小鼠模型中 NK 细胞的发育和功能受损，因此很难研究体内急性和慢性 HIV 感染期间不同组织中 NK 细胞的发育和免疫反应。在本期 JCI 中，Sangur 等人。报告了转基因 MSTRG-6-15 小鼠模型，其中将人 IL-6 和 IL-15 敲入先前构建的 MSTRG 小鼠中。前身模型缺乏 Rag2 和 γ 链 (γc)，敲入表达人 M-CSF、IL-3、GM-CSF 和 TPO，以及转基因表达人 SIRPα。研究人员研究了 HIV 感染期间的组织特异性 NK 细胞免疫反应，并清楚地表明，人源化小鼠模型中的内源性人类 NK 细胞抑制了 HIV-1 体内的复制。这些发现为利用先天免疫反应进行临床抗病毒治疗提供了见解。
NK cells are an important subset of innate immune effectors with antiviral activity. However, NK cell development and immune responses in different tissues during acute and chronic HIV infection in vivo have been difficult to study due to the impaired development and function of NK cells in conventional humanized mouse models. In this issue of the JCI, Sangur et al. report on a transgenic MISTRG-6-15 mouse model with human IL-6 and IL-15 knocked into the previously constructed MISTRG mice. The predecessor model was deficient in Rag2 and γ chain (γc) with knock-in expression of human M-CSF, IL-3, GM-CSF, and TPO, and transgenic expression of human SIRPα. The researchers studied tissue–specific NK cell immune responses during HIV infection and clearly show that the endogenous human NK cells in the humanized mouse model suppressed HIV-1 replication in vivo. These findings provide insight into harnessing the innate immune response for clinical antiviral therapies.