Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Immunity. 2015 Dec 15;43(6):1174-85. doi: 10.1016/j.immuni.2015.10.017. Epub 2015 Dec 8.
The central nervous system (CNS) is an immunologically privileged site protected from uncontrolled access of T cells by the blood-brain barrier (BBB), which is breached upon autoimmune inflammation. Here we have shown that receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) on T cells regulates C-C type chemokine ligand 20 (CCL20) production by astrocytes and T cell localization in the CNS. Importantly, mice specifically lacking RANKL in T cells were resistant to experimental autoimmune encephalomyelitis (EAE) due to altered T cell trafficking. Pharmacological inhibition of RANKL prevented the development of EAE without affecting the peripheral immune response, indicating that RANKL is a potential therapeutic target for treating autoimmune diseases in the CNS.
中枢神经系统（CNS）是一个免疫特权部位，通过血脑屏障（BBB）来保护其免受 T 细胞的失控进入，而自身免疫炎症会破坏血脑屏障。在这里，我们已经表明 T 细胞上的核因子-κB（NF-κB）受体激活剂（RANKL）调节星形胶质细胞产生 C-C 型趋化因子配体 20（CCL20）和 T 细胞在中枢神经系统中的定位。重要的是，由于 T 细胞迁移的改变，特异性缺乏 T 细胞上 RANKL 的小鼠对实验性自身免疫性脑脊髓炎（EAE）具有抗性。RANKL 的药理学抑制作用可预防 EAE 的发生，而不影响外周免疫反应，表明 RANKL 是治疗 CNS 自身免疫性疾病的潜在治疗靶点。
