CCR4控制调节性T细胞的空间分布及其对自身免疫性疾病的作用

Regulatory T cells play an essential role in preventing autoimmune diseases, which is dependent on their spatial positioning in lymphoid tissues. Our published study indicated that regulatory T cells suppress auto-reactive T cell activation by clustering tightly around dendritic cells. However, the underlying mechanisms involved in forming such a distribution pattern remain largely unexplored. Interestingly, our new data show that CCR4-high regulatory T cells migrated to and clustered around dendritic cells, which expressed CCL22. This result reveals the correlation between CCR4 and regulatory T cell distribution in lymphoid tissues. Therefore, we will address the following questions: 1. The impact of CCR4 on regulatory T cell suppressive function in vivo; 2. The role of CCR4 on regulatory T cells in the autoimmune disease model. 3. The molecular mechanisms of CCR4 expression in regulatory T cells. Hopefully, this study will provide new targets and strategies for the treatment of autoimmune diseases.

调节性T细胞 (Treg细胞) 对于抑制自身免疫性疾病的发生起着关键作用，而其功能的发挥与它们在淋巴组织里的空间分布有密切的关系。我们已发表的工作显示，Treg细胞主要通过和树突状细胞相互作用、并在其周围形成“细胞集落”的形式来抑制自身反应性T细胞的激活。但是，有哪些机制调控该空间分布的形成，目前知之甚少。有趣的是，我们的最新数据表明，树突状细胞通过分泌CCL22招募高表达CCR4的Treg细胞聚集在其周围形成细胞集落。这一结果揭示了CCR4与淋巴组织中Treg细胞空间分布的关联性。因此，我们将研究如下科学问题：1. CCR4对Treg细胞发挥抑制性功能的作用；2. 高表达CCR4的Treg细胞在自身免疫性疾病模型中的作用；3. 调控Treg细胞表达CCR4的分子机制。阐明这些问题将为我们从调控Treg细胞空间分布的角度治疗自身免疫性疾病提供新的靶点和策略。