CCDC134 ameliorated experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells
CCDC134 ameliorated experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells
复制标题
DOI：
10.1016/j.bbi.2018.03.015
复制
发表时间：
2018-07-01
影响因子：
15.1
通讯作者：
Huang, Jing
中科院分区：
文献类型：
--
作者：
Xia, Peng;Gong, Xiaoting;Huang, Jing
CCDC 134（coiled-coil domain containing 134）是一种类精氨酸分子，以前曾报道通过增强CD 8（+）T细胞介导的免疫而发挥抗肿瘤作用。然而，脊髓中CCDC 134表达模式的动态变化可能与实验性自身免疫性脑脊髓炎（EAE）（多发性硬化症的动物模型）的进展有关，目前尚不清楚。在这项研究中，我们发现CCDC 134的表达在脊髓EAE的进展过程中显着增加。此外，我们证明了CCDC 134显著降低了EAE的严重程度并减缓了其进展，这与脊髓炎症和脱髓鞘减少有关。CCDC 134诱导效应的潜在机制涉及通过调节JAK/STAT信号传导抑制辅助性T细胞（Th）-1和Th 17细胞分化及其关键效应分子IFN-γ和IL-17 A的分泌。这些发现表明，CCDC 134通过靶向关键信号通路选择性调节致病性Thl和Th 17细胞而发挥有效的抗炎作用。该研究为CCDC 134作为治疗自身免疫性疾病的独特治疗剂的作用提供了见解。(C)2018爱思唯尔公司All rights reserved.
CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule, was previously reported to exert antitumor effects by augmenting CD8(+) T-cell mediated immunity. However, the dynamic changes in CCDC134 expression patterns in the spinal cord that may be involved in the progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, remains unclear. In this study, we found that CCDC134 expression was markedly increased in the spinal cord during the progression of EAE. Furthermore, we demonstrated that CCDC134 significantly reduced the severity and slowed the progression of EAE, which correlated with reduced spinal cord inflammation and demyelination. The underlying mechanism of CCDC134-induced effects involved inhibition of T helper (Th)-1 and Th17 cell differentiation and secretion of its key effector molecules IFN-gamma and IL-17A via regulation of JAK/STAT signaling. These findings indicate that CCDC134 exerts potent anti-inflammatory effects through the selective modulation of pathogenic Thl and Th17 cells by targeting critical signaling pathways. The study provides insights into the role of CCDC134 as a unique therapeutic agent for the treatment of autoimmune diseases. (C) 2018 Elsevier Inc. All rights reserved.