Downregulation of TCF1 in HIV Infection Impairs T-cell Proliferative Capacity by Disrupting Mitochondrial Function.
Downregulation of TCF1 in HIV Infection Impairs T-cell Proliferative Capacity by Disrupting Mitochondrial Function.
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HIV 感染中 TCF1 的下调会破坏线粒体功能，从而损害 T 细胞增殖能力
DOI：
10.3389/fmicb.2022.880873
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管抗逆转录病毒疗法（ART）对艾滋病毒感染者有好处，但t细胞功能障碍不能完全恢复。代谢失调与hiv -1特异性t细胞功能障碍有关。探索调节代谢适应性的因素有助于逆转t细胞功能障碍，并为其潜在机制提供新的见解。在这项研究中，hiv感染者和hiv阴性对照（nc）被纳入。采用定量逆转录聚合酶链反应和流式细胞术检测细胞中t细胞因子（TCF）1的表达。分析GEO数据库的相关微阵列数据，探讨其潜在机制。体外观察TCF1对t细胞功能和代谢功能的影响。与长期非进展个体和nc相比，快速进展者外周血单个核细胞中TCF7 mRNA表达下调。与nc相比，treatment-naïve hiv感染者CD4+和CD8+ t细胞上的TCF1表达下调。TCF1敲除的t细胞白细胞介素（IL）2的产生和增殖能力受损。此外，TCF1敲低的t细胞糖酵解能力和线粒体呼吸功能下降，TCF1敲低的t细胞去极化线粒体增加。HIV感染中TCF1的下调通过破坏线粒体功能损害t细胞增殖能力。这些发现强调了代谢调节是TCF1调节t细胞功能障碍的关键机制。
Despite the benefits of antiretroviral therapy (ART) for people with HIV, T-cell dysfunction cannot be fully restored. Metabolic dysregulation is associated with dysfunction of HIV-1-specific T-cells. Exploration of the factors regulating metabolic fitness can help reverse T-cell dysfunction and provide new insights into the underlying mechanism. In this study, HIV-infected individuals and HIV-negative control individuals (NCs) were enrolled. T-cell factor (TCF)1 expression in cells was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry. Relevant microarray data from the GEO database were analyzed to explore the underlying mechanism. The effects of TCF1 on T-cell function and metabolic function were assessed in vitro. TCF7 mRNA expression in peripheral blood mononuclear cells was downregulated in rapid progressors compared with long-term non-progressors individuals and NCs. TCF1 expression on CD4+ and CD8+ T-cells was downregulated in treatment-naïve HIV-infected individuals compared with NCs. Interleukin (IL)2 production and proliferative capacity were impaired in TCF1 knockdown T-cells. Moreover, glycolytic capacity and mitochondrial respiratory function were decreased in TCF1 knockdown T-cells, and depolarized mitochondria were increased in TCF1 knockdown T-cells. Downregulation of TCF1 in HIV infection impairs T-cell proliferative capacity by disrupting mitochondrial function. These findings highlight the metabolic regulation as a pivotal mechanism of TCF1 in the regulation of T-cell dysfunction.
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影响因子：
24.8
作者：
Escobar G;Mangani D;Anderson AC
通讯作者：
Anderson AC
DOI：
10.1073/pnas.1110230108
发表时间：
2011-12-13
影响因子：
11.1
作者：
Germar, Kristine;Dose, Marei;Gounari, Fotini
通讯作者：
Gounari, Fotini
影响因子：
8
作者：
Rutishauser, Rachel L.;Deguit, Christian Deo T.;Hunt, Peter W.
通讯作者：
Hunt, Peter W.
影响因子：
32.4
作者：
Gabriel, Sarah S.;Tsui, Carlson;Kallies, Axel
通讯作者：
Kallies, Axel
影响因子：
64.5
作者：
Buck MD;Sowell RT;Kaech SM;Pearce EL
通讯作者：
Pearce EL