IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis
IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis
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DOI：
10.1073/pnas.0802218105
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发表时间：
2008-07-01
影响因子：
11.1
通讯作者：
Naka, Tetsuji
中科院分区：
文献类型：
--
作者：
Serada, Satoshi;Fujimoto, Minoru;Naka, Tetsuji
Th 17细胞的发育是实验性自身免疫性脑脊髓炎（EAE）发病机制中的关键事件，EAE是人类多发性硬化（MS）的小鼠模型。先前的研究已经证明，IL-6依赖性途径参与了Th 17细胞从初始CD 4阳性T细胞的体外分化。然而，IL-6在EAE中体内Th 17细胞发育中的作用仍不清楚。在本研究中，我们发现用抗IL-6受体单克隆抗体（抗IL-6 R mAb）治疗IL-6阻断剂可抑制EAE的发生，并抑制腹股沟淋巴结中髓鞘少突胶质细胞糖蛋白（MOG）肽特异性CD 4阳性、CD 8阳性和Th 17 T细胞的诱导。因此，IL-6阻断在EAE中的保护作用可能通过抑制MOG肽特异性Th 17细胞和Th 1细胞的发育来介导，这反过来导致T细胞向CNS中的浸润减少。这些结果表明，抗IL-6 R mAb治疗可能代表了一种治疗人类MS的新疗法。
The development of Th17 cells is a key event in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis (MS). Previous studies have demonstrated that an IL-6-dependent pathway is involved in the differentiation of Th17 cells from naive CD4-positive T cells in vitro. However, the role of IL-6 in vivo in the development of Th17 cells in EAE has remained unclear. In the present study, we found that IL-6 blockade by treatment with an anti-IL-6 receptor monoclonal antibody (anti-IL-6R mAb) inhibited the development of EAE and inhibited the induction of myelin oligodendrocyte glycoprotein (MOG) pepticle-specific CD4-positive, CD8-positive, and Th17 T cells, in inguinal lymph nodes. Thus, the protective effect of IL-6 blockade in EAE is likely to be mediated via the inhibition of the development of MOG-peptide-specific Th17 cells and Th1 cells, which in turn leads to reduced infiltration of T cells into the CNS. These findings indicate that anti-IL-6R mAb treatment might represent a novel therapy for human MS.