A Critical Role for IL-21 Receptor Signaling in the Coxsackievirus B3-Induced Myocarditis

被引:0
作者
Fan Yang
Xiao-mou Wei
Wen-wu Liang
Wen-hong Mo
Bao-ping Tan
Hong Wang
机构
[1] The Fourth Affiliated Hospital of Guangxi Medical University/Liuzhou Workers’ Hospital,Department of Cardiology
来源
Inflammation | 2017年 / 40卷
关键词
IL-21 receptor; coxsackievirus B3; myocarditis;
D O I
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学科分类号
摘要
To determine whether IL-21 receptor signaling plays a significant role in promoting Tfh cell-mediated cardiac injury in viral myocarditis (VMC), we compared IL-21R-deficient mice for some parameters of VMC. Balb/c and IL-21R−/− mice were infected with CVB3. Frequencies of splenic Tfh cells were determined by flow cytometric analysis, and productions of anti-adenine nucleotide translocator (ANT) autoantibodies were detected by enzyme-linked immunosorbent assay. To determine the effects of IL-21R signal on the proliferation of B cells, lymphocytes from spleens of the IL-21R−/− and Balb/c mice infected by CVB3 were tagged with carboxyfluorescein succinimidyl ester (CFSE) and then were stimulated with lipopolysaccharides plus IL-21 or anti-IL-21 neutralizing antibody for 3 days. The proliferation of B cells was analyzed by flow cytometry. Anti-ANT antibodies in the supernatants were detected by ELISA. Results showed that IL-21R−/− mice developed significantly less inflammation of the myocardium than Balb/c mice. Numbers of the Tfh cells and levels of anti-ANT antibody were decreased in IL-21R−/− mice, indicating IL-21 signaling plays a role on the Tfh cell response. The percentage of CD19+CFSE+ B cells decreased in IL-21R−/− mice compared to VMC mice. And anti-ANT antibodies were detected at lower levels in cultured supernatant from IL-21R−/− mice than in those from VMC mice. These data suggest that IL-21R signal may contribute to anti-ANT antibody production and expansion of B cells in VMC mice.
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页码:1428 / 1435
页数:7
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共 165 条
[1]  
Blauwet LA(2010)Myocarditis Progress in Cardiovascular Diseases 52 274-288
[2]  
Cooper LT(2007)Coxsackievirus-induced myocarditis in mice: a model of autoimmune disease for studying immunotoxicity Methods 41 118-122
[3]  
Fairweather D(2006)T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17 The Journal of Experimental Medicine 203 2009-2019
[4]  
Rose NR(2008)CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis Journal of Immunology 180 2686-2695
[5]  
Rangachari M(2011)Expression of IL-23/Th17 pathway in a murine model of coxsackie virus B3-induced viral myocarditis Virology Journal 8 301-137
[6]  
Mauermann N(2011)Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation Virology Journal 8 17-766
[7]  
Marty RR(2012)Increased expressions of IL-22 and Th22 cells in the coxsackievirus B3-induced mice acute viral myocarditis Virology Journal 9 232-1523
[8]  
Dirnhofer S(2008)A fundamental role for interleukin-21 in the generation of T follicular helper cells Immunity 29 127-1155
[9]  
Kurrer MO(2008)T follicular helper (TFH) cells in normal and dysregulated immune responses Annual Review of Immunology 26 741-1163
[10]  
Komnenovic V(2009)A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice Proceedings of the National Academy of Sciences of the United States of America 106 1518-5955