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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >SAMHD1's protein expression profile in humans
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SAMHD1's protein expression profile in humans

机译：SAMHD1在人类中的蛋白质表达谱

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摘要

The deoxynucleoside triphosphate triphosphohydrolase and 3'-> 5' exonuclease SAMHD1 restricts HIV-1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue-resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV-susceptible CD4(+) T cells carried pSAMHD1(T592), whereas resting CD4(+) T cells and macrophages expressed the unphosphorylated protein with HIV-restrictive activity. Surprisingly, stimulation of these primary cells with IFN-alpha, IFN-gamma, IL-4, IL-6, IL-12, IL-18, IL-27, or TNF-alpha affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL-1 beta moderately down-regulated SAMHD1 in activated CD4(+) T cells. Taken together, this study establishes the first cross-sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle-dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines.
机译：脱氧核苷三磷酸三磷酸水解酶和3'-> 5'核酸外切酶SAMHD1限制了非循环造血细胞在体外的HIV-1感染，而SAMHD1突变与AGS相关。关于该细胞因子的体内表达和功能调节知之甚少。在这里，我们首先在来自> 210个供体的25个人体组织的微阵列上以及纯化的原代细胞群中评估了SAMHD1蛋白的表达谱。在体内，SAMHD1在造血起源的大多数有核细胞中表达，包括组织驻留巨噬细胞，DC，pDC，胸腺T细胞，单核细胞，NK细胞的所有发育阶段，以及在B细胞中的较低水平。值得注意的是，SAMHD1在生殖器粘膜中的HIV靶细胞中大量表达，为评估其作为可能影响HIV传播效率的细胞因子提供了基础。接下来，我们检查了细胞的激活状态和促炎细胞因子处理对SAMHD1表达和磷酸化的影响。激活的，对HIV敏感的CD4（+）T细胞携带pSAMHD1（T592），而静止的CD4（+）T细胞和巨噬细胞则表达具有HIV限制性活性的未磷酸化蛋白。令人惊讶地，用IFN-α，IFN-γ，IL-4，IL-6，IL-12，IL-18，IL-27或TNF-α刺激这些原代细胞既不影响SAMHD1表达水平也不影响苏氨酸592磷酸化。在激活的CD4（+）T细胞中只有IL-1β适度下调SAMHD1。综上所述，这项研究建立了人类组织中SAMHD1的第一个横截面蛋白表达谱，并提供了其依赖于细胞周期的磷酸化和对多种促炎细胞因子无反应的见解。

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