Ablation of IL-17 expression moderates experimental autoimmune myasthenia gravis disease severity
Ablation of IL-17 expression moderates experimental autoimmune myasthenia gravis disease severity
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DOI：
10.1016/j.cyto.2017.05.008
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发表时间：
2017-08-01
期刊：
影响因子：
3.8
通讯作者：
Kaminski, Henry J.
中科院分区：
文献类型：
--
作者：
Aguilo-Seara, Gabriela;Xie, Yanchen;Kaminski, Henry J.
一系列细胞因子影响早发性重症肌无力 (MG) 及其动物模型实验性自身免疫性重症肌无力 (EAMG) 的发病机制。重症肌无力患者，尤其是那些虚弱程度较严重的患者，血液中促炎细胞因子 IL-17 升高。我们通过在敲除 IL-17 的小鼠中诱导 EAMG 来评估 IL-17A 在自身免疫中的作用，发现 EAMG 严重程度有所降低，但并未完全消除疾病。 IL-17k 小鼠没有虚弱、乙酰胆碱受体抗体水平低以及乙酰胆碱受体保留在神经肌肉接头处的证据。 EAMG IL-17k 小鼠的脾脏生发中心尺寸减小，同时 Foxp3 和 BCL-6 基因表达升高，表明促炎信号的转变。结果强调了 IL-17 在 EAMG 发育中的重要性，以及 IL-17 独立途径驱动自身免疫反应。
An array of cytokines influences the pathogenesis of early onset myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG). Patients with MG, in particular those with more severe weakness, have elevations of the pro-inflammatory cytokine IL-17 in the blood. We assessed the role of IL-17A in autoimmunity by inducing EAMG in mice with knockout of IL-17 and found a reduction of EAMG severity, but not a complete ablation of disease. The IL-17k mice had no evidence of weakness, low levels of acetylcholine receptor antibodies, and retention of acetylcholine receptor at the neuromuscular junction. Splenic germinal center size was reduced in EAMG IL-17k mice along with elevations of Foxp3 and BCL-6 gene expression, suggesting a shift away from pro-inflammatory signals. The results emphasize the importance of IL-17 in EAMG development and that IL-17 independent pathways drive the autoimmune reaction.