Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis

Th17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Theref...

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Main Authors: Qi Long, Yu-Hua Liao, Yu Xie, Wei Liang, Xiang Cheng, Jing Yuan, Miao Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-12-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fcimb.2016.00171/full
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author Qi Long
Yu-Hua Liao
Yu Xie
Wei Liang
Xiang Cheng
Jing Yuan
Miao Yu
author_facet Qi Long
Yu-Hua Liao
Yu Xie
Wei Liang
Xiang Cheng
Jing Yuan
Miao Yu
author_sort Qi Long
collection DOAJ
description Th17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Therefore, we investigated whether Nup98 mediated Th17 cell differentiation in AVMC. In our study, patients with AVMC and healthy controls were recruited. The results showed that CVB3 could enter into the CD4+ T cells in AVMC patients and healthy controls. After transfecting purified CD4+ T cells with CVB3 in vitro, the Th17 cell frequency, IL-17 secretion, and RORγT synthesis were increased while the Nup98 levels were decreased. Furthermore, down-regulating Nup98 expression by siRNA-Nup98 in CD4+ T cells resulted in the elevated Th17 cell frequency and IL-17 secretion, along with enhanced levels of RORγT, dissociative p300/CBP, and acetylated Stat3. Up-regulation of Nup98 expression by pcDNA3.1-Nup98 showed the opposite effects. Our results suggested that CVB3 directly induced CD4+ T cell differentiation into Th17 cells by inhibiting Nup98 expression, representing a therapeutic target in AVMC.
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spelling doaj.art-282011b9b8504ce8a01ba89af96c075e2022-12-21T23:26:40ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882016-12-01610.3389/fcimb.2016.00171231496Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditisQi Long0Yu-Hua Liao1Yu Xie2Wei Liang3Xiang Cheng4Jing Yuan5Miao Yu6Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyTh17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Therefore, we investigated whether Nup98 mediated Th17 cell differentiation in AVMC. In our study, patients with AVMC and healthy controls were recruited. The results showed that CVB3 could enter into the CD4+ T cells in AVMC patients and healthy controls. After transfecting purified CD4+ T cells with CVB3 in vitro, the Th17 cell frequency, IL-17 secretion, and RORγT synthesis were increased while the Nup98 levels were decreased. Furthermore, down-regulating Nup98 expression by siRNA-Nup98 in CD4+ T cells resulted in the elevated Th17 cell frequency and IL-17 secretion, along with enhanced levels of RORγT, dissociative p300/CBP, and acetylated Stat3. Up-regulation of Nup98 expression by pcDNA3.1-Nup98 showed the opposite effects. Our results suggested that CVB3 directly induced CD4+ T cell differentiation into Th17 cells by inhibiting Nup98 expression, representing a therapeutic target in AVMC.http://journal.frontiersin.org/Journal/10.3389/fcimb.2016.00171/fullTh17 CellsNUP98Coxsackievirus B3Viral myocarditisCoxsackie-adenovirus receptor
spellingShingle Qi Long
Yu-Hua Liao
Yu Xie
Wei Liang
Xiang Cheng
Jing Yuan
Miao Yu
Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis
Frontiers in Cellular and Infection Microbiology
Th17 Cells
NUP98
Coxsackievirus B3
Viral myocarditis
Coxsackie-adenovirus receptor
title Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis
title_full Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis
title_fullStr Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis
title_full_unstemmed Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis
title_short Coxsackievirus B3 directly induced Th17 cell differentiation by inhibiting Nup98 expression in patients with acute viral myocarditis
title_sort coxsackievirus b3 directly induced th17 cell differentiation by inhibiting nup98 expression in patients with acute viral myocarditis
topic Th17 Cells
NUP98
Coxsackievirus B3
Viral myocarditis
Coxsackie-adenovirus receptor
url http://journal.frontiersin.org/Journal/10.3389/fcimb.2016.00171/full
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