Neutralization of IL-17 inhibits the production of anti-ANT autoantibodies in CVB3-induced acute viral myocarditis.
Anti-adenine nucleotide translocator (ANT) autoantibodies are related to the development of Coxsackievirus B3 (CVB3)-triggered acute viral myocarditis (AVMC). Recently, studies suggested that IL-17 especially produced by a novel CD4(+) Th-cell subset Th17 cells contributed to the production of pathogenic autoantibodies in some autoimmune diseases. However, the pathogenic role of IL-17 in AVMC remains largely unknown. In this study, we investigated whether IL-17 was associated with the disease progression and the production of anti-ANT autoantibodies in AVMC mouse model. The results showed that IL-17 monoclonal antibody (mAb)-treated AVMC mice had decreased HW/BW, reduced serum CK-MB activity and improved pathological score of heart sections along with the reduction of circulating IL-17 level and serum anti-ANT autoantibodies. The correlation index of serum IL-17 concentration and anti-ANT-autoantibody level was 0.874, p<0.01. In addition, the experimental results in vitro further proved that IL-17mAb could inhibit the proliferation of CD19(+) B lymphocytes and the secretion of anti-ANT autoantibodies. Our data suggested that IL-17 was related to the disease progression in AVMC mouse model by regulating the production of autoantibodies and blocking IL-17 might represent a promising novel therapeutic approach.
Yuan
Jing
J
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
Yu
Miao
M
Lin
Qiong-Wen
QW
Cao
Ai-Lin
AL
Yu
Xian
X
Dong
Ji-Hua
JH
Wang
Jin-Ping
JP
Zhang
Jing-Hui
JH
Wang
Min
M
Guo
He-Ping
HP
Liao
Yu-Hua
YH
D033741:Adenine Nucleotide Translocator 1 / Q000276:immunology*; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000821:virology*
D033741:Adenine Nucleotide Translocator 1; D019138:Antibodies, Blocking; D001323:Autoantibodies; D020381:Interleukin-17