Faculty of Medicine, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Division of Neurology, Department of Clinical Neurosciences, Neuroimmunology Laboratory, Geneva University Hospital, Geneva, Switzerland; Division of Laboratory Medicine, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland.
Eur J Immunol. 2014 Jan;44(1):46-57. doi: 10.1002/eji.201242985. Epub 2013 Oct 1.
The innate Toll-like receptor 7 (TLR7) detects infections by recognizing viral and bacterial single-stranded RNA. In addition to pathogen-derived RNA, immune cells expressing high levels of TLR7, such as B cells and dendritic cells (DCs), can be activated by self-RNA. During myelin-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, TLR7 expression is increased within the central nervous system (CNS). To define the contribution of TLR7 to the development of EAE, we evaluated the course of the disease in C57BL/6-Tlr7-deficient mice compared with that in WT mice and found that TLR7-deficient mice had decreased disease severity. This protection was associated with decreased myelin oligodendrocyte glycoprotein-specific T-cell activation by primed DCs, decreased circulating autoantibodies, attenuated inflammation within the CNS, and increased Foxp3(+) regulatory T cells in the periphery and in the CNS. In conclusion, we show that TLR7 is involved in the maintenance of autoimmunity in the pathogenesis of EAE.
先天 Toll 样受体 7（TLR7）通过识别病毒和细菌的单链 RNA 来检测感染。除了病原体衍生的 RNA 之外，表达高水平 TLR7 的免疫细胞，如 B 细胞和树突状细胞（DC），也可以被自身 RNA 激活。在实验性自身免疫性脑脊髓炎（EAE）期间，多发性硬化症的动物模型中，中枢神经系统（CNS）内 TLR7 的表达增加。为了确定 TLR7 对 EAE 发展的贡献，我们评估了与 WT 小鼠相比 TLR7 缺陷型 C57BL/6 小鼠的疾病过程，发现 TLR7 缺陷型小鼠的疾病严重程度降低。这种保护与致敏 DC 引起的少突胶质细胞髓鞘糖蛋白特异性 T 细胞激活减少、循环自身抗体减少、CNS 内炎症减轻以及外周和 CNS 中 Foxp3(+)调节性 T 细胞增加有关。总之，我们表明 TLR7 参与了 EAE 发病机制中自身免疫的维持。
