title: Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis.
abstract: 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 CVB3in 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.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003384:Coxsackievirus Infections / Q000097:blood / Q000821:virology*; D004770:Enterovirus / Q000302:isolation & purification / Q000472:pathogenicity*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D008214:Lymphocytes / Q000821:virology; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000821:virology*; D028861:Nuclear Pore Complex Proteins / Q000187:drug effects* / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; D058504:Th17 Cells / Q000821:virology*; D055815:Young Adult
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D020381:Interleukin-17; D028861:Nuclear Pore Complex Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C465451:Nup98 protein, human; D050796:STAT3 Transcription Factor
keywords: Nup98; Th17 cells; coxsackie-adenovirus receptor; coxsackievirus B3; viral myocarditis