Regulatory T cells (Tregs) are indispensable for the maintenance of immunological self-tolerance and homeostasis. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is required for optimal Treg induction. Here, we reveal that human-induced Tregs (iTregs) lacking hnRNPA1 show reduced expression of the transcription factor FOXP3, increased ubiquitination level of FOXP3, and impaired suppressive abilities. Human naïve CD4 T cells with hnRNPA1 knockdown show a decreased Treg differentiation ratio. hnRNPA1 could interact with FOXP3 as well as with the E3 ligase Stub1. The phosphorylation at hnRNPA1 S199 could increase both interactions. The overexpression of FOXP3 in Tregs containing shhnRNPA1 could not recover the phenotype caused by hnRNPA1 knockdown. Therefore, there might be multiple essential pathways regulated by hnRNPA1 in Tregs. In conclusion, we present a new role of hnRNPA1 in promoting Treg function, indicating it as a promising target for tumor therapies.

中文翻译：

---

hnRNPA1 增强 FOXP3 稳定性以促进调节性 T 细胞的分化和功能

调节性 T 细胞 (Tregs) 对于维持免疫自我耐受和体内平衡是必不可少的。最佳 Treg 诱导需要异质核核糖核蛋白 A1 (hnRNPA1)。在这里，我们揭示了缺乏 hnRNPA1 的人类诱导的 Tregs (iTregs) 表现出转录因子 FOXP3 的表达降低、FOXP3 泛素化水平增加和抑制能力受损。具有 hnRNPA1 敲低的人类幼稚 CD4 T 细胞显示 Treg 分化率降低。hnRNPA1 可以与 FOXP3 以及 E3 连接酶 Stub1 相互作用。hnRNPA1 S199 的磷酸化可以增加这两种相互作用。FOXP3 在含有 shhnRNPA1 的 Treg 中的过表达无法恢复由 hnRNPA1 敲低引起的表型。因此，Tregs 中可能存在多种受 hnRNPA1 调控的重要途径。综上所述，