Mechanism of Th17 cell differentiation in acute viral myocarditis induced by Coxsackievirus B3
10.3969/j.issn.1000-484X.2025.09.021
- VernacularTitle:柯萨奇病毒B3诱导的急性病毒性心肌炎中Th17细胞分化的机制研究
- Author:
Jianan WANG
1
;
Huilan LIU
;
Jiantao ZHENG
;
Wei WANG
;
Tingpei ZHUANG
;
Jiexiang HUANG
;
Jiadong FU
Author Information
1. 福建省泉州市第一医院心血管内科,泉州 362000
- Publication Type:Journal Article
- Keywords:
Coxsackievirus B3;
Acute viral myocarditis;
TLR7;
IL-6;
Th17;
Cell differentiation
- From:
Chinese Journal of Immunology
2025;41(9):2179-2184
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the potential mechanism underlying IL-6 production through the TLR7 signaling pathway,which regulates Th17 cell differentiation in the context of Coxsackievirus B3(CVB3)-induced acute viral myocarditis(AVMC).Meth-ods:A total of 110 patients diagnosed with AVMC were admitted to Quanzhou First Hospital,Fujian between January 2020 and Janu-ary 2023,alongside 93 healthy volunteers.CD4+T cells were isolated from the subjects'blood,and the levels of CVB3 and the number of Th17 cells were assessed.Subsequently,CD4+T cells were infected with CVB3,and the levels of Th17 cells,IL-17,IL-21,and TNF-α were measured.After knockdown of TLR7 or treatment with TLR7 inhibitors,the differentiation of CVB3-infected CD4+T cells into Th17 cells was observed.Results:In comparison to healthy controls,AVMC patients exhibited elevated plasma levels of hsCRP,IL-17,IL-21,and TNF-α(P<0.05).The levels of CVB3 mRNA in CD4+T cells were also notably higher in AVMC patients compared to healthy controls(P<0.05).The mean viral titer in AVMC patients measured 230 PFU/ml,while no detectable virus was found in healthy volunteers(P<0.05).In CD4+T cells,the count of Th17 cells was significantly increased in AVMC patients compared to healthy volunteers(P<0.05).Moreover,the number of Th17 cells in peripheral blood CD4+T cells of AVMC patients showed a positive correlation with CVB3 virus titer(P<0.05).Following CVB3 infection,the number of Th17 cells increased compared with the control group(P<0.05),accompanied by elevated levels of IL-17,IL-21,and TNF-α in the supernatant(P<0.05).Knockdown of TLR7 and CVB3 infection in CD4+T cells significantly reduced the levels of Th17 cells(P<0.05),while the expression level of phosphorylated-activated TLR7 increased significantly after CVB3 infection of CD4+T cells compared to the control group(P<0.05).Treatment with the TLR7 inhibitor M5049 and CVB3 infection led to a significant decrease in Th17 cell levels(P<0.05).The secretion of IL-6 in CD4+T cells increased after CVB3 infection(P<0.05),and this increase was mitigated by TLR7 knockdown and CVB3 infection(P<0.05)as well as TLR7 inhibitor M5049 treatment and CVB3 infection(P<0.05).Conclusion:CVB3 activates TLR7 via phosphoryla-tion,prompting CD4+T cells to release IL-6 and undergo differentiation into Th17 cells.Consequently,TLR7 emerges as a promising therapeutic target for AVMC.
