Small molecule-mediated upregulation of CCR7 ameliorates murine experimental autoimmune encephalomyelitis by accelerating T-cell homing
Small molecule-mediated upregulation of CCR7 ameliorates murine experimental autoimmune encephalomyelitis by accelerating T-cell homing
复制标题
小分子介导的 CCR7 上调通过加速 T 细胞归巢来改善小鼠实验性自身免疫性脑脊髓炎
DOI：
10.1016/j.intimp.2017.10.004
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发表时间：
2017
影响因子：
5.6
通讯作者：
Xu Qiang
中科院分区：
文献类型：
--
作者：
Li Xin;Lu Tingting;Xue Wenwen;Wang Yixuan;Luo Qiong;Ge Huiming;Tan Renxiang;Shen Yan;Xu Qiang
抑制免疫细胞向中枢神经系统的浸润是抑制多发性硬化症（MS）及其实验性自身免疫性脑脊髓炎（EAE）动物模型发展的一个有前途的靶点。在这里，我们发现口服合成的小分子化合物Fc 24对EAE的发展显示出潜在的预防作用，包括降低EAE的严重程度和延迟疾病的发作。Fc24促进CD 4+和CD 8 +T细胞在脾脏和淋巴结内的积聚，而对MOG特异性T细胞反应没有影响。此外，体内和体外活化T细胞上的Fc24上调CCR7表达，伴随着经处理的T细胞中响应于CCL19的ERK活化。这些发现表明，小分子介导的CCR7上调可能通过促进T细胞归巢到淋巴器官内来改善EAE，并且Fc 24可能是修饰EAE发展的潜在候选者。
Impairing the infiltration of immune cells into the CNS is a promising target for suppressing the development of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Here, we found that oral administration of a synthetic small molecular compound Fc24 showed potential preventive effects on the development of EAE, including the reduction in EAE severity and a delay in the onset of the disease. Fc24 facilitated the accumulation of both CD4+and CD8+T cells within spleen and lymph nodes, while having no effect on MOG-specific T cell responses. Furthermore, CCR7 expression was upregulated by Fc24 on activated T cellsin vivoandin vitro, accompanied by ERK activation in the treated T cells in response to CCL19. These findings demonstrate that small molecule-mediated CCR7 upregulation might ameliorate EAE by facilitating T cell homing into and within lymphoid organs, and that Fc24 may be a potential candidate for modifying the development of EAE.