LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection.
LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection.
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LNCRNA HOTAIRM1在HCV感染期间通过HOXA1-MIR124轴促进MDSC的扩展和抑制功能。
DOI：
10.1038/s41598-020-78786-1
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发表时间：
2020-12-16
影响因子：
4.6
通讯作者：
Yao ZQ
中科院分区：
文献类型：
--
作者：
Thakuri BKC;Zhang J;Zhao J;Nguyen LN;Nguyen LNT;Khanal S;Cao D;Dang X;Schank M;Wu XY;Morrison ZD;Gazzar ME;Li Z;Jiang Y;Ning S;Wang L;Moorman JP;Yao ZQ
HOXA转录反义RNA髓系特异性1(HOTAIRM1)是一种长的非编码RNA(LncRNA)，通过靶向HOXA1基因的表达，在调节髓系细胞的发育中发挥关键作用。我们和其他人之前已经证明，髓系来源的抑制细胞(MDSCs)是一种不同种类的未成熟髓系细胞，在慢性病毒(丙型肝炎病毒、艾滋病病毒)感染期间会扩张。然而，HOTAIRM1在病毒感染期间MDSCs的发展和抑制中的作用仍不清楚。在这项研究中，我们证明HOTAIRM1及其靶标HOXA1的表达显著上调，以促进来自丙型肝炎病毒(HCV)感染患者的CD33+髓系细胞中免疫抑制分子的表达，包括精氨酸酶1、诱导型一氧化氮合酶、信号转导和转录激活因子3以及活性氧物种。我们发现，丙型肝炎病毒相关外切体(HCV-Exo)可以调节HOTAIRM1、HOXA1和miR124的表达，从而调节MDSC的发育。重要的是，HOTAIRM1或HOXA1在健康CD33+髓系细胞中的过表达促进了MDSC的分化和抑制功能，相反，沉默HOTAIRM1或HOXA1在丙型肝炎患者MDSC中的表达显著降低了MDSC的频率及其抑制功能。本质上，这些结果表明HOTAIRM1-HOXA1-miR124轴增强了MDSCs的分化和抑制功能，并可能成为慢性病毒感染期间免疫调节和抗病毒治疗的潜在靶点。
HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is a long non-coding RNA (lncRNA) that plays a pivotal role in regulating myeloid cell development via targeting HOXA1 gene expression. We and others have previously shown that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells, expand during chronic viral (HCV, HIV) infections. However, the role of HOTAIRM1 in the development and suppression of MDSCs during viral infection remains unknown. In this study, we demonstrate that the expressions of HOTAIRM1 and its target HOXA1 are substantially upregulated to promote the expressions of immunosuppressive molecules, including arginase 1, inducible nitric oxide synthase, signal transducer and activator of transcription 3, and reactive oxygen species, in CD33+ myeloid cells derived from hepatitis C virus (HCV)-infected patients. We show that HCV-associated exosomes (HCV-Exo) can modulate HOTAIRM1, HOXA1, and miR124 expressions to regulate MDSC development. Importantly, overexpression of HOTAIRM1 or HOXA1 in healthy CD33+ myeloid cells promoted the MDSC differentiation and suppressive functions; conversely, silencing of HOTAIRM1 or HOXA1 expression in MDSCs from HCV patients significantly reduced the MDSC frequency and their suppressive functions. In essence, these results indicate that the HOTAIRM1-HOXA1-miR124 axis enhances the differentiation and suppressive functions of MDSCs and may be a potential target for immunomodulation in conjunction with antiviral therapy during chronic viral infection.
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DOI：
10.1084/jem.20090831
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Han YC;Park CY;Bhagat G;Zhang J;Wang Y;Fan JB;Liu M;Zou Y;Weissman IL;Gu H
通讯作者：
Gu H
影响因子：
6.4
作者：
Cheng, Yong Q.;Ren, Jun P.;Yao, Zhi Q.
通讯作者：
Yao, Zhi Q.
影响因子：
5.4
作者：
Masciopinto, F;Giovani, C;Abrignani, S
通讯作者：
Abrignani, S
lncRNA HOTAIRM1通过增强自噬途径调节PML-RARA癌蛋白的降解和骨髓细胞分化
影响因子：
12.4
作者：
Chen ZH;Wang WT;Huang W;Fang K;Sun YM;Liu SR;Luo XQ;Chen YQ
通讯作者：
Chen YQ
影响因子：
6.7
作者：
Bowers NL;Helton ES;Huijbregts RP;Goepfert PA;Heath SL;Hel Z
通讯作者：
Hel Z