Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis.
Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis.
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柯萨奇病毒 B3 通过抑制急性病毒性心肌炎患者的 Nup98 表达直接诱导 Th17 细胞分化。
DOI：
10.3389/fcimb.2016.00171
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发表时间：
2016
影响因子：
5.7
通讯作者：
Yu M
中科院分区：
文献类型：
--
作者：
Long Q;Liao YH;Xie Y;Liang W;Cheng X;Yuan J;Yu M
Th17细胞在柯萨奇病毒B3 （CVB3）诱导的急性病毒性心肌炎（AVMC）的进展中起关键作用。然而，病毒对Th17细胞分化的直接影响尚不清楚。近年来，核孔蛋白（Nup） 98已被证实与淋巴细胞分化有关。因此，我们研究了Nup98是否介导了AVMC中Th17细胞的分化。在我们的研究中，我们招募了AVMC患者和健康对照组。结果表明，CVB3可以进入AVMC患者和健康对照的CD4+ T细胞。体外用CVB3转染纯化的CD4+ T细胞后，Th17细胞频率增加，IL-17分泌增多，RORγT合成减少，Nup98水平降低。此外，siRNA-Nup98在CD4+ T细胞中下调Nup98的表达，导致Th17细胞频率和IL-17分泌升高，RORγT、解离性p300/CBP和乙酰化Stat3水平升高。pcDNA3.1-Nup98上调Nup98的表达则表现出相反的效果。我们的研究结果表明，CVB3通过抑制Nup98的表达，直接诱导CD4+ T细胞向Th17细胞分化，这是AVMC的一个治疗靶点。
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 CVB3 in 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.
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影响因子：
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作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
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Littman, Dan R.
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