Distinct Th17 inductions contribute to the gender bias in CVB3-induced myocarditis
Distinct Th17 inductions contribute to the gender bias in CVB3-induced myocarditis
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不同的 Th17 诱导导致了 CVB3 诱导的心肌炎的性别偏见。
DOI：
10.1016/j.carpath.2013.02.004
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发表时间：
2013-09-01
影响因子：
3.7
通讯作者：
Xiong, Sidong
中科院分区：
文献类型：
--
作者：
Li, Zhenping;Yue, Yan;Xiong, Sidong
背景：病毒性心肌炎常由柯萨奇病毒B3（CVB 3）感染引起，且多见于男性。到目前为止，这种性别差异的机制还没有完全阐明。Th 17细胞作为一种新的促炎性T细胞群，在CVB 3诱导的心肌炎的发生发展中起重要作用，但其对病毒性心肌炎性别偏倚的影响尚不清楚。方法：采用CVB 3腹腔感染雄性和雌性小鼠，7 d后比较脾脏Th 17细胞的频率及相关细胞因子和转录因子的表达。结果：CVB 3感染后，雄性小鼠Th 17细胞频率明显升高，且明显高于雌性小鼠。相应地，相关的细胞因子和转录因子的表达也在雄性中明显增强。当用单克隆抗体中和IL-17时，心肌炎的男性患病率明显消除，进一步证实了Th 17细胞在病毒性心肌炎性别偏倚中的作用。雌二醇在体外和体内均能显著抑制CVB 3感染后Th 17细胞的分化。结论：雌激素对CVB 3诱导的Th 17细胞分化的抑制作用主要表现在男性，而女性则相反，这可能是导致CVB 3诱导的心肌炎敏感性性别差异的重要原因。本研究有助于我们了解Th 17细胞在病毒性心肌炎中的作用，并有助于制定相应的治疗策略。(c)2013 Elsevier Inc. All rights reserved.
Background: Viral myocarditis is often caused by coxsackievirus B3 (CVB3) infection and occurs more frequently in males. So far, the mechanisms for this sex difference are not fully elucidated. As a new proinflammatory T cell population, Th17 cells are required for the development of CVB3-induced myocarditis, but their impact on the gender bias in viral myocarditis is still unknown.Methods: Male and female mice were intraperitoneally infected with CVB3; 7 days later, the frequency of splenic Th17 cells and the expression of associated cytokines and transcriptional factors were compared. Meanwhile, the impact of sex hormones on Th17 cell differentiation post CVB3 infection was also evaluated.Results: In infected male mice, Th17 cell frequency was remarkably increased and significantly higher than that in female mice. Accordingly, the expression of associated cytokines and transcriptional factors was also obviously augmented in males. When neutralizing interleukin-17 by monoclonal antibody, the male prevalence of myocarditis was obviously abolished, further confirming the effect of Th17 cells on gender bias in viral myocarditis. It was also found that estradiol significantly inhibited the Th17 differentiation post CVB3 infection both in vitro and in vivo. However, testosterone showed no such effects.Conclusions: Th17 cells were predominantly induced in CVB3-infected males than females as the inhibitory effect of estrogen on Th17 differentiation and played an important role in the sex differences in the sensitivity to CVB3-induced myocarditis. This study may help us understand the role of Th17 cells in viral myocarditis and facilitate the development of corresponding therapeutic strategies. (c) 2013 Elsevier Inc. All rights reserved.