LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection

Abstract 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 heterogene...

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Autores principales:	Bal Krishna Chand Thakuri, Jinyu Zhang, Juan Zhao, Lam N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Dechao Cao, Xindi Dang, Madison Schank, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Zhengke Li, Yong Jiang, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4a3ec38509049228aa48ba468be63bc
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spelling	oai:doaj.org-article:a4a3ec38509049228aa48ba468be63bc2021-12-02T13:34:00ZLncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection10.1038/s41598-020-78786-12045-2322https://doaj.org/article/a4a3ec38509049228aa48ba468be63bc2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78786-1https://doaj.org/toc/2045-2322Abstract 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.Bal Krishna Chand ThakuriJinyu ZhangJuan ZhaoLam N. NguyenLam N. T. NguyenSushant KhanalDechao CaoXindi DangMadison SchankXiao Y. WuZheng D. MorrisonMohamed El GazzarZhengke LiYong JiangShunbin NingLing WangJonathan P. MoormanZhi Q. YaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bal Krishna Chand Thakuri Jinyu Zhang Juan Zhao Lam N. Nguyen Lam N. T. Nguyen Sushant Khanal Dechao Cao Xindi Dang Madison Schank Xiao Y. Wu Zheng D. Morrison Mohamed El Gazzar Zhengke Li Yong Jiang Shunbin Ning Ling Wang Jonathan P. Moorman Zhi Q. Yao LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection
description	Abstract 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.
format	article
author	Bal Krishna Chand Thakuri Jinyu Zhang Juan Zhao Lam N. Nguyen Lam N. T. Nguyen Sushant Khanal Dechao Cao Xindi Dang Madison Schank Xiao Y. Wu Zheng D. Morrison Mohamed El Gazzar Zhengke Li Yong Jiang Shunbin Ning Ling Wang Jonathan P. Moorman Zhi Q. Yao
author_facet	Bal Krishna Chand Thakuri Jinyu Zhang Juan Zhao Lam N. Nguyen Lam N. T. Nguyen Sushant Khanal Dechao Cao Xindi Dang Madison Schank Xiao Y. Wu Zheng D. Morrison Mohamed El Gazzar Zhengke Li Yong Jiang Shunbin Ning Ling Wang Jonathan P. Moorman Zhi Q. Yao
author_sort	Bal Krishna Chand Thakuri
title	LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection
title_short	LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection
title_full	LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection
title_fullStr	LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection
title_full_unstemmed	LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection
title_sort	lncrna hotairm1 promotes mdsc expansion and suppressive functions through the hoxa1-mir124 axis during hcv infection
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/a4a3ec38509049228aa48ba468be63bc
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LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection

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