Department of Neurology, the First Hospital of Jilin University, Changchun, China; Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Scand J Immunol. 2014 Sep;80(3):180-90. doi: 10.1111/sji.12201.
Experimental autoimmune neuritis (EAN), an animal model of human Guillain-Barré syndrome, has long been considered as a T helper (Th) 1 cell-mediated autoimmune disorder. However, deficiency of IFN-γ, a signature Th1 cytokine, aggravated EAN, with features of elevated production of IL-17A, despite an alleviated systemic Th1 immune response. We hypothesized that Th17 cells and their cytokines might play a pathogenic role in EAN. To further clarify the roles of these Th and regulatory T cell (Treg) cytokines in the pathogenesis of EAN and their interrelationship, we investigated the expression of Th1/Th2/Th17/Treg cytokines in EAN in this study. We found that the levels of Th17 cells and IL-17A in cauda equina (CE)-infiltrating cells and splenic mononuclear cells (MNCs) as well as in serum paralleled the disease evolution, which increased progressively during the initiation stage and reached higher value at the peak of EAN. The same pattern was also noticed for the expression of IL-22. The diverse expression profiles of FoxP3, IL-17 receptors A and C were seen in CE-infiltrating cells and splenic MNCs in EAN. These findings indicate a major pro-inflammatory role of Th17 cells and IL-17A in the pathogenesis of EAN. Therapeutic interventions may be focused upon inhibiting Th17 cells and their cytokines in the early phase of EAN, so as to delay and suppress clinical signs of the disease, which has relevance for future studies on pathogenesis and treatment of GBS in humans.
实验性自身免疫性神经炎（EAN），一种人类格林-巴利综合征的动物模型，长期以来被认为是 T 辅助（Th）1 细胞介导的自身免疫性疾病。然而，IFN-γ（一种标志性的 Th1 细胞因子）的缺乏加重了 EAN，尽管系统性 Th1 免疫反应减轻，但 IL-17A 的产生增加。我们假设 Th17 细胞及其细胞因子可能在 EAN 发病机制中发挥致病作用。为了进一步阐明这些 Th 和调节性 T 细胞（Treg）细胞因子在 EAN 发病机制中的作用及其相互关系，我们在本研究中研究了 EAN 中 Th1/Th2/Th17/Treg 细胞因子的表达。我们发现，尾神经根（CE）浸润细胞和脾单核细胞（MNC）以及血清中 Th17 细胞和 IL-17A 的水平与疾病演变平行，在启动阶段逐渐增加，在 EAN 的高峰期达到更高值。IL-22 的表达也呈现出相同的模式。EAN 中 CE 浸润细胞和脾 MNC 中 FoxP3、IL-17 受体 A 和 C 的表达呈现出多样化的表达谱。这些发现表明 Th17 细胞和 IL-17A 在 EAN 发病机制中发挥主要的促炎作用。治疗干预可能集中在抑制 EAN 早期的 Th17 细胞及其细胞因子上，以延迟和抑制疾病的临床症状，这对人类格林-巴利综合征的发病机制和治疗的未来研究具有相关性。
