背景:CD4⁺CD25⁺Foxp3⁺调节性 T 细胞(Tregs)在维持免疫稳态中起着不可或缺的 作用。由于 Tregs 使用的多种机制需要与靶细胞的密切接触，Tregs 免疫抑制功能的 实现依赖于其在特定位置的分布，然而，调控 Tregs 迁移的上游调节因子仍不清楚。

方法:我们通过构建多聚嘧啶结合蛋白 1(Ptbp1)在 Tregs 中特定敲除的条件性 敲除鼠，对小鼠进行体征观察，淋巴细胞亚群以及各组织 Tregs 的分布的分析。通过 体外试验鉴定 Tregs 的功能，增殖，凋亡，稳定性和活化,探索 Ptbp1 特异性敲除的 Tregs 功能缺陷，进而通过竞争性移植模型和黑色素肿瘤模型验证，进一步确定 Ptbp1 在 Tregs 中的重要作用。

结果:在这里，我们证明 Ptbp1 可以通过调控各种迁移/趋化相关分子来调节 Tregs 从淋巴结迁移到各组织。与野生型小鼠相比，Tregs 特异性 Ptbp1 缺失的小鼠表现出 明显的生长发育障碍和免疫紊乱。Ptbp1 缺陷的 Tregs 在外周淋巴结中选择性积累， 而在非淋巴组织，特别是皮肤和骨髓中的比例减少。外周淋巴结中的 Tregs 的抑制能 力、稳定性、凋亡和增殖能力没有显著的受损。进一步，我们发现 Tregs 中的 Ptbp1 缺陷导致多种迁移/趋化相关分子的异常表达，包括 CD44、CXCR4 和 CCR4，从而阻碍 了 Tregs 从淋巴结中迁出。此外，Tregs 中的 Ptbp1 缺失可增强对皮肤黑色素瘤小鼠 的抗肿瘤免疫。

结论:Ptbp1 是调节 Tregs 迁移的重要调节因子，Ptbp1 可能是肿瘤治疗中的一个 有希望的治疗靶点。 

Background: CD4+CD25+Foxp3+ regulatory T cells (Tregs) play an indispensable role in maintaining immune homeostasis. The realization of the immunosuppressive function of Treg cells relies on the appropriate localization because the multiple mechanisms that Treg cells use require proximity to the target cells. However, the upstream regulators governing the migration of Treg remain unclear.

Methods: We constructed conditioned knockout mice with specific knockout of polypyrimidine binding protein 1 (Ptbp1) in Tregs, and analyzed the physical signs, lymphocyte subsets, and the distribution of Tregs in each tissue of the mice. The function, proliferation, apoptosis, stability and activation of Tregs were identified through in vitro experiments, and the functional defects of Tregs specifically knocked out by Ptbp1 were explored, and the important role of Ptbp1 in Tregs was further confirmed by competitive transplantation model and melanin tumor model.

Result: Here, we demonstrate that Polypyrimidine tract-binding protein 1 (Ptbp1) can regulate the migration of Tregs via various trafficking molecules. Mice with Tregs-specific deletion of Ptbp1 develop significant immune disorders. Tregs with Ptbp1 deficiency selectively accumulate in the lymph nodes with decreased frequencies in non-lymphoid tissues, especially in skin and bone marrow. The suppressive capacity, stability, apoptosis, and proliferation ability of Tregs in lymph nodes are not impaired. Ptbp1 deficiency in Tregs resulted in abnormal expression of multiple trafficking molecules, including CD44, CXCR4, and CCR4, impeding the egress of Tregs from LNs. Besides, Ptbp1 deletion in Tregs can enhance antitumor immunity in mice with skin melanoma.