Regulatory T cells (Tregs) play a significant role in limiting damage of tissue affected by autoimmune process, which has been demonstrated in various experimental models for multiple sclerosis (MS) (mostly experimental autoimmune encephalomyelitis – EAE), rheumatoid arthritis, and type 1 diabetes. In this study, we demonstrated that Tregs increasingly migrate to central nervous system (CNS) during subsequent phases of EAE (preclinical, initial attack, and remission). In contrast, in peripheral tissues (blood, lymph nodes, and spleen), a significant accumulation of Tregs is mostly present during EAE remission. Moreover, an increased expression of CCR6 on Tregs in the CNS, blood, lymph nodes, and spleen in all phases of EAE was observed. The highest expression of CCR6 on Tregs from the CNS, lymph nodes, and spleen was noted during the initial attack of EAE, whereas in the blood, the peak expression of CCR6 was detected during the preclinical phase. The presence of Tregs in the CNS during EAE was confirmed by immunohistochemistry. To analyze additional functional significance of CCR6 expression on Tregs for EAE pathology, we modulated the clinical course of this MS model using Tregs with blocked CCR6. EAE mice, which received CCR6-deficient Tregs showed significant amelioration of disease severity. This observation suggests that CCR6 on Tregs may be a potential target for future therapeutic interventions in MS.

中文翻译：

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CCR6对调节性T细胞的阻断改善了多发性硬化症的实验模型

调节性T细胞（Tregs）在限制受自身免疫过程影响的组织损伤中起着重要作用，这已在多发性硬化症（MS）（主要是实验性自身免疫性脑脊髓炎– EAE），类风湿性关节炎和1型糖尿病的各种实验模型中得到证实。在这项研究中，我们证明了Tregs在EAE的后续阶段（临床前，初始发作和缓解）逐渐迁移至中枢神经系统（CNS）。相反，在外周组织（血液，淋巴结和脾脏）中，EAE缓解期间大部分存在Treg的大量积累。而且，在EAE的所有阶段中，观察到CCR6在CNS，血液，淋巴结和脾脏中的Treg上的表达增加。CCR6在中枢神经系统，淋巴结，在EAE初次发作时注意到脾脏和脾脏，而在血液中，在临床前期检测到CCR6的峰值表达。通过免疫组织化学证实EAE期间CNS中Treg的存在。为了分析TCR上CCR6表达对于EAE病理的其他功能意义，我们使用带有封闭CCR6的Treg调节了该MS模型的临床过程。接受CCR6缺陷型Treg的EAE小鼠显示出疾病严重程度的明显改善。该观察结果表明，Tregs上的CCR6可能是MS未来治疗干预的潜在靶标。为了分析TCR上CCR6表达对于EAE病理的其他功能意义，我们使用带有封闭CCR6的Treg调节了该MS模型的临床过程。接受CCR6缺陷型Treg的EAE小鼠显示出疾病严重程度的明显改善。该观察结果表明，Tregs上的CCR6可能是MS未来治疗干预的潜在靶标。为了分析TCR上CCR6表达对于EAE病理的其他功能意义，我们使用带有封闭CCR6的Treg调节了该MS模型的临床过程。接受CCR6缺陷型Treg的EAE小鼠显示出疾病严重程度的明显改善。该观察结果表明，Tregs上的CCR6可能是MS未来治疗干预的潜在靶标。