Phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein PINLYP regulates type I interferon innate immunity.
Phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein PINLYP regulates type I interferon innate immunity.
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磷脂酶A2抑制剂和LY6/PLAUR结构域蛋白PINLYP调节I型干扰素先天免疫
DOI：
10.1073/pnas.2111115119
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发表时间：
2022-01-04
影响因子：
11.1
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Liu Z;Jiang C;Lei Z;Dong S;Kuang L;Huang C;Gao Y;Liu M;Xiao H;Legembre P;Jung JU;Liang H;Liang X
干扰素(干扰素)介导的抗病毒反应是宿主抵抗病毒感染的先天免疫防御的第一线。在这里，我们发现了一个未知的蛋白质，命名为磷脂酶A2抑制因子和LY6/PLAUR结构域包含蛋白(PINLYP)，它是胚胎发育所必需的，在I型干扰素抗病原体感染中起着重要作用。PINLYP缺陷损害了I型干扰素的产生，并抑制了体内宿主对DNA和RNA病毒感染的防御。我们揭示了I型干扰素先天免疫中的一个独特因素，以及抗病毒治疗的潜在靶点。I型干扰素(I型干扰素)是宿主对入侵病原体的先天免疫反应的第一前线。在此，我们鉴定了一种由磷脂酶A2抑制剂和含LY6/PLAUR结构域的基因(PINLYP)编码的未知蛋白，它与TBK1相互作用，并以依赖于TBK1和IRF3的方式诱导I型干扰素。在多种细胞类型中，PINLYP的缺失可抑制DNA病毒、核糖核酸病毒和各种Toll样受体配体诱导的IRF3的激活和干扰素-β的产生。因为小鼠缺乏PINLYP会导致小鼠早期胚胎死亡，所以我们产生了一只条件小鼠，在条件小鼠中，PINLYP缺乏树突状细胞。在树突状细胞中缺乏PINLYP的小鼠在诱导I型干扰素方面存在缺陷，更容易受到致命性病毒的感染。因此，PINLYP是I型干扰素先天免疫的正调节因子，对宿主有效防御病毒感染具有重要意义。
Significance Interferon (IFN)-mediated antiviral responses serve as the first line of the host innate immune defense against viral infection. Here we identify a previously uncharacterized protein designated phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein (PINLYP), which is essential for embryonic development and plays an important role in type I IFN against pathogen infection. PINLYP deficiency impairs type I IFN production and dampens in vivo host defense against DNA and RNA virus infection. We unravel a unique actor in the type I IFN innate immunity and a potential target for the antiviral therapies. Type I interferons (IFNs) are the first frontline of the host innate immune response against invading pathogens. Herein, we characterized an unknown protein encoded by phospholipase A2 inhibitor and LY6/PLAUR domain-containing (PINLYP) gene that interacted with TBK1 and induced type I IFN in a TBK1- and IRF3-dependent manner. Loss of PINLYP impaired the activation of IRF3 and production of IFN-β induced by DNA virus, RNA virus, and various Toll-like receptor ligands in multiple cell types. Because PINLYP deficiency in mice engendered an early embryonic lethality in mice, we generated a conditional mouse in which PINLYP was depleted in dendritic cells. Mice lacking PINLYP in dendritic cells were defective in type I IFN induction and more susceptible to lethal virus infection. Thus, PINLYP is a positive regulator of type I IFN innate immunity and important for effective host defense against viral infection.
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RIG-I 样受体的免疫信号传导。
影响因子：
32.4
作者：
Loo YM;Gale M Jr
通讯作者：
Gale M Jr
影响因子：
64.5
作者：
Ng CT;Mendoza JL;Garcia KC;Oldstone MB
通讯作者：
Oldstone MB
影响因子：
4.5
作者：
Loughner CL;Bruford EA;McAndrews MS;Delp EE;Swamynathan S;Swamynathan SK
通讯作者：
Swamynathan SK
DOI：
10.1098/rspb.1957.0049
发表时间：
1957-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
ISAACS, A;LINDENMANN, J;VALENTINE, RC
通讯作者：
VALENTINE, RC
影响因子：
30.3
作者：
Dobbs N;Burnaevskiy N;Chen D;Gonugunta VK;Alto NM;Yan N
通讯作者：
Yan N